chemicallytechFine Chemical TechnologiesТонкие химические технологии2410-65932686-7575MIREA – Russian Technological University (RTU MIREA).10.32362/2410-6593-2021-16-4-287-306chemicallytech-1724Research ArticleCHEMISTRY AND TECHNOLOGY OF ORGANIC SUBSTANCESХИМИЯ И ТЕХНОЛОГИЯ ОРГАНИЧЕСКИХ ВЕЩЕСТВStructure and biological action of analogs and derivatives of biogenic polyaminesСтруктура и биологическое действие аналогов и производных биогенных полиаминовhttps://orcid.org/0000-0003-1930-8227ЕгоровО. С.EgorovO. S.

Егоров Олег Сергеевич, магистр кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова

119571, Москва, пр-т Вернадского, д. 86

ResearcherID AAW-7636-2020

 

Oleg S. Egorov, Master Student, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies

86, Vernadskogo pr., Moscow, 119571

Scopus Author ID 8880163900

egorov1997@inbox.ruhttps://orcid.org/0000-0002-7316-8109БорисоваН. Ю.BorisovaN. Yu.

Борисова Надежда Юрьевна, к.х.н., доцент кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова

119571, Москва, пр-т Вернадского, д. 86

Scopus Author ID 55780738100

Nadezhda Yu. Borisova, Cand. Sci. (Chem.), Associate Professor, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies

86, Vernadskogo pr., Moscow, 119571

Scopus Author ID 55780738100

ladask714485@yandex.ruhttps://orcid.org/0000-0002-8122-3577БорисоваЕ. Я.BorisovaE. Ya.

Борисова Елена Яковлевна, д.х.н., профессор кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова

119571, Москва, пр-т Вернадского, д. 86

Scopus Author ID 8880163900

Elena Ya. Borisova, Dr. Sci. (Chem.), Professor, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies

86, Vernadskogo pr., Moscow, 119571

Scopus Author ID 8880163900

helen-bor714485@yandex.ruhttps://orcid.org/0000-0002-5393-913XРежаббаевМ. Л.RezhabbaevM. L.

Режаббаев Музаффар Латибжонович, аспирант кафедры химии и технологии биологически активных соединений, медицинской и органической химии им. Н.А. Преображенского Института тонких химических технологий им. М.В. Ломоносова

119571, Москва, пр-т Вернадского, д. 86

Muzaffar L. Rezhabbaev, Postgraduate Student, N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies

86, Vernadskogo pr., Moscow, 119571

Rezhabbayev@gmail.comhttps://orcid.org/0000-0002-5620-4649АфанасьеваЕ. Ю.Afanas’evaE. Yu.

Афанасьева Елена Юльевна, к.м.н., ведущий научный сотрудник

121552, Москва, ул. 3-я Черепковская, д. 15а

Elena Yu. Afanas’eva, Cand. Sci. (Med.), Leading Researcher, National Medical Research Center of Cardiology

15a, 3 Cherepkovskaya ul., Moscow, 121552

embroilment@gmail.comhttps://orcid.org/0000-0002-1270-3067АрзамасцевЕ. В.ArzamastsevE. V.

Арзамасцев Евгений Вениаминович, д.м.н., профессор, заведующий лаборатории лекарственной токсикологии

121552, Москва, ул. 3-я Черепковская, д. 15а

Evgeny V. Arzamastsev, Dr. Sci. (Med.), Professor, Head of the Laboratory of Drug Toxicology, National Medical Research Center of Cardiology

15a, 3 Cherepkovskaya ul., Moscow, 121552

arz4146931@yandex.ruМИРЭА – Российский технологический университет (Институт тонких химических технологий им. М.В. Ломоносова)РоссияMIREA – Russian Technological UniversityRussian FederationНациональный медицинский исследовательский центр кардиологии Министерства здравоохранения РФРоссияNational Medical Research Center of Cardiology, Ministry of Health of the Russian FederationRussian Federation202128092021164287306Copyright © Egorov O.S., Borisova N.Y., Borisova E.Y., Rezhabbaev M.L., Afanas’eva E.Y., Arzamastsev E.V., 20212021Егоров О.С., Борисова Н.Ю., Борисова Е.Я., Режаббаев М.Л., Афанасьева Е.Ю., Арзамасцев Е.В.Egorov O.S., Borisova N.Y., Borisova E.Y., Rezhabbaev M.L., Afanas’eva E.Y., Arzamastsev E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.finechem-mirea.ru/jour/article/view/1724

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.

Цели. Биогенные полиамины широко представлены в живой природе. Они характерны как для клеток простейших, так и для многоклеточных организмов. Данные соединения обладают широким спектром биологической активности и необходимы для нормального роста и развития клеток. Нарушение гомеостаза полиаминов может вызывать существенные отклонения в функционировании клетки, провоцируя протекание патологических процессов различного рода, включая онкологические и психоневрологические заболевания. Воздействие на «полиаминовый путь» является привлекательным базисом для создания ряда фармакологически активных веществ с различным спектром действия. Целью данного обзора является обобщение результатов исследований, посвященных изучению биологической активности соединений полиаминового ряда; сопоставление биологического действия с воздействием на определенные молекулярные мишени. В виду структурного многообразия данной группы веществ невозможно в полной мере отразить имеющиеся на сегодняшний момент данные в одном обзоре. Поэтому в настоящей работе основное внимание уделено производным насыщенных полиаминов ациклического строения.Результаты. В общем виде рассмотрены следующие аспекты: биологическая активность, биосинтез и катаболизм, клеточный транспорт и локализация биогенных полиаминов в живых системах. Представлены структурные аналоги и производные биогенных полиаминов, обладающие противоопухолевой, нейропротекторной, антиаритмической, противопаразитарной, антибактериальной и некоторыми другими видам биологической активности; отражена взаимосвязь между биологической активностью и мишенями воздействия. Установлено, что на характер воздействия большое влияние оказывает природа заместителя, количество катионных центров, а также длина полиаминовой цепи.Выводы. В настоящее время применение структур полиаминового ряда сдерживается наличием цитотоксичности, а также неспецифического токсического воздействия на ЦНС. Дальнейшие исследования в области биохимии, клеточного транспорта, а также более глубокое понимание механизмов рецепторного взаимодействия позволят использовать полиамины в качестве основы для создания потенциальных лекарственных препаратов.

полиаминыбиогенные аминыпутресцинпроизводные полиаминовсперминспермидинбиосинтез полиаминовкатаболизм полиаминовтранспорт полиаминовантиаритмическая активностьантибактериальная активностьпротивоопухолевая активностьаналоги полиаминовнейродегенеративные заболеванияpolyaminesbiogenic aminesputrescinepolyamine derivativessperminespermidinepolyamine biosynthesispolyamine catabolismpolyamine transportantiarrhythmic activityantibacterial activityantitumor activitypolyamine analogsneurodegenerative diseasesReferencesShoji T., Hashimoto T. Polyamine-Derived Alkaloids in Plants: Molecular Elucidation of Biosynthesis. In: Polyamines: A Universal Molecular Nexus for Growth, Survival, and Specialized Metabolism. Tokyo, Japan: Springer; 2015. P. 189–200. https://doi.org/10.1007/978-4-431-55212-3_16Shoji T., Hashimoto T. Polyamine-Derived Alkaloids in Plants: Molecular Elucidation of Biosynthesis. In: Polyamines: A Universal Molecular Nexus for Growth, Survival, and Specialized Metabolism. Tokyo, Japan: Springer; 2015. P. 189–200. https://doi.org/10.1007/978-4-431-55212-3_16Kachel H.S., Buckingham S.D., Sattelle D.B. Insect toxins–selective pharmacological tools and drug/chemical leads. Curr. Opin. Insect. Sci. 2018;30:93–98. https://doi.org/10.1016/j.cois.2018.10.001Kachel H.S., Buckingham S.D., Sattelle D.B. Insect toxins–selective pharmacological tools and drug/chemical leads. Curr. Opin. Insect. Sci. 2018;30:93–98. https://doi.org/10.1016/j.cois.2018.10.001Fujiwara T., Hasegawa S., Hirashima N., Nakanishi M., Ohwada T. Gene transfection activities of amphiphilic steroid–polyamine conjugates. Biochim. Biophys. Acta. Biomembr. 2000;1468(1–2):396–402. https://doi.org/10.1016/S0005-2736(00)00278-9Fujiwara T., Hasegawa S., Hirashima N., Nakanishi M., Ohwada T. Gene transfection activities of amphiphilic steroid–polyamine conjugates. Biochim. Biophys. Acta. Biomembr. 2000;1468(1–2):396–402. https://doi.org/10.1016/S0005-2736(00)00278-9Menzi M., Lightfoot H.L., Hall J. Polyamine– oligonucleotide conjugates: a promising direction for nucleic acid tools and therapeutics. Future Med. Chem. 2015;7(13):1733–1749. https://doi.org/10.4155/fmc.15.90Menzi M., Lightfoot H.L., Hall J. Polyamine– oligonucleotide conjugates: a promising direction for nucleic acid tools and therapeutics. Future Med. Chem. 2015;7(13):1733–1749. https://doi.org/10.4155/fmc.15.90Pegg A.E. Functions of polyamines in mammals. J. Biol. Chem. 2016;291(29):14904–14912. https://doi.org/10.1074/jbc.r116.731661Pegg A.E. Functions of polyamines in mammals. J. Biol. Chem. 2016;291(29):14904–14912. https://doi.org/10.1074/jbc.r116.731661Bachrach U. Naturally occurring polyamines: interaction with macromolecules. Curr. Protein Pept. Sci. 2005;6(6):559–566. https://doi.org/10.2174/138920305774933240Bachrach U. Naturally occurring polyamines: interaction with macromolecules. Curr. Protein Pept. Sci. 2005;6(6):559–566. https://doi.org/10.2174/138920305774933240D’Agostino L., Di Pietro M., Di Luccia A. Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation. The FEBS J. 2005;272(15):3777–3787. https://doi.org/10.1111/j.1742-4658.2005.04782.xD’Agostino L., Di Pietro M., Di Luccia A. Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation. The FEBS J. 2005;272(15):3777–3787. https://doi.org/10.1111/j.1742-4658.2005.04782.xDouki T., Bretonniere Y., Cadet J. Protection against radiation-induced degradation of DNA bases by polyamines. Radiat. Res. 2000;153(1):29–35. https://doi.org/10.1667/0033-7587(2000)153[0029:PARIDO]2.0.CO;2Douki T., Bretonniere Y., Cadet J. Protection against radiation-induced degradation of DNA bases by polyamines. Radiat. Res. 2000;153(1):29–35. https://doi.org/10.1667/0033-7587(2000)153[0029:PARIDO]2.0.CO;2Rudolphi-Szydło E., Filek M., Dyba B., Miszalski Z., Zembala M. Antioxidative action of polyamines in protection of phospholipid membranes exposed to ozone stress. Acta Biochim. Pol. 2020;67(2):259–262. https://doi.org/10.18388/abp.2020_5230Rudolphi-Szydło E., Filek M., Dyba B., Miszalski Z., Zembala M. Antioxidative action of polyamines in protection of phospholipid membranes exposed to ozone stress. Acta Biochim. Pol. 2020;67(2):259–262. https://doi.org/10.18388/abp.2020_5230Rosenheim O. The isolation of spermine phosphate from semen and testis. Biochem. J. 1924;18(6):1253–1262. https://doi.org/10.1042/bj0181253Rosenheim O. The isolation of spermine phosphate from semen and testis. Biochem. J. 1924;18(6):1253–1262. https://doi.org/10.1042/bj0181253Bachrach U. The early history of polyamine research. Plant Physiol. Biochem. 2010;48(7):490–495. https://doi.org/10.1016/j.plaphy.2010.02.003Bachrach U. The early history of polyamine research. Plant Physiol. Biochem. 2010;48(7):490–495. https://doi.org/10.1016/j.plaphy.2010.02.003Michael A.J. Polyamines in eukaryotes, bacteria, and archaea. J. Biol. Chem. 2016;291(29):14896–14903. https://doi.org/10.1074/jbc.R116.734780Michael A.J. Polyamines in eukaryotes, bacteria, and archaea. J. Biol. Chem. 2016;291(29):14896–14903. https://doi.org/10.1074/jbc.R116.734780Kuksa V., Buchan R., Lin P. K.T. Synthesis of polyamines, their derivatives, analogues and conjugates. Synthesis. 2000;2000(09):1189–1207. https://doi.org/10.1055/s-2000-6405Kuksa V., Buchan R., Lin P. K.T. Synthesis of polyamines, their derivatives, analogues and conjugates. Synthesis. 2000;2000(09):1189–1207. https://doi.org/10.1055/s-2000-6405Gupta K., Dey A., Gupta B. Plant polyamines in abiotic stress responses. Acta Physiol. Plant. 2015;35(7):2015–2036. https://doi.org/10.1007/s11738-013-1239-4Gupta K., Dey A., Gupta B. Plant polyamines in abiotic stress responses. Acta Physiol. Plant. 2015;35(7):2015–2036. https://doi.org/10.1007/s11738-013-1239-4Urdiales J.L., Medina M.A., Sanchez-Jimenez F. Polyamine metabolism revisited. Eur. J. Gastroenterol. Hepatol. 2001;13(9):1015–1019. https://doi.org/10.1097/00042737-200109000-00003Urdiales J.L., Medina M.A., Sanchez-Jimenez F. Polyamine metabolism revisited. Eur. J. Gastroenterol. Hepatol. 2001;13(9):1015–1019. https://doi.org/10.1097/00042737-200109000-00003Mimitsuka T., Sawai H., Hatsu M., Yamada K. Metabolic engineering of Corynebacterium glutamicum for cadaverine fermentation. Biosci. Biotechnol. Biochem. 2007;71(9):2130–2135. https://doi.org/10.1271/bbb.60699Mimitsuka T., Sawai H., Hatsu M., Yamada K. Metabolic engineering of Corynebacterium glutamicum for cadaverine fermentation. Biosci. Biotechnol. Biochem. 2007;71(9):2130–2135. https://doi.org/10.1271/bbb.60699Chou, H.T., Li, J.Y., Peng, Y.C., Lu, C.D. Molecular characterization of PauR and its role in control of putrescine and cadaverine catabolism through the γ-glutamylation pathway in Pseudomonas aeruginosa PAO1. J. Bacteriol. 2013;195(17):3906–3913. https://doi.org/10.1128/jb.00275-13Chou, H.T., Li, J.Y., Peng, Y.C., Lu, C.D. Molecular characterization of PauR and its role in control of putrescine and cadaverine catabolism through the γ-glutamylation pathway in Pseudomonas aeruginosa PAO1. J. Bacteriol. 2013;195(17):3906–3913. https://doi.org/10.1128/jb.00275-13Konishi H., Nakajima T., Sano I. Metabolism of putrescine in the central nervous system. J. Biochem. 1977;81(2):355–360. https://doi.org/10.1093/oxfordjournals.jbchem.a131466Konishi H., Nakajima T., Sano I. Metabolism of putrescine in the central nervous system. J. Biochem. 1977;81(2):355–360. https://doi.org/10.1093/oxfordjournals.jbchem.a131466Casero Jr R.A., Pegg A.E. Spermidine/spermine N1-acetyltransferase—the turning point in polyamine metabolism. Faseb J. 1993;7(8):653–66. https://doi.org/10.1096/fasebj.7.8.8500690Casero Jr R.A., Pegg A.E. Spermidine/spermine N1-acetyltransferase—the turning point in polyamine metabolism. Faseb J. 1993;7(8):653–66. https://doi.org/10.1096/fasebj.7.8.8500690Vujcic S., Diegelman P., Bacchi C.J., Kramer D.L., Porter C.W. Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem. J. 2002;367(3):665–675. https://doi.org/10.1042/bj20020720Vujcic S., Diegelman P., Bacchi C.J., Kramer D.L., Porter C.W. Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem. J. 2002;367(3):665–675. https://doi.org/10.1042/bj20020720Takao K., Sugita Y. Pentamine as a Substrate for Measuring Spermine Oxidase Activity. In: Polyamines: Methods and Protocols. New York, USA: Humana Press; 2018. P. 149–154. https://doi.org/10.1007/978-1-4939-7398-9_15Takao K., Sugita Y. Pentamine as a Substrate for Measuring Spermine Oxidase Activity. In: Polyamines: Methods and Protocols. New York, USA: Humana Press; 2018. P. 149–154. https://doi.org/10.1007/978-1-4939-7398-9_15Casero Jr R.A., Pegg A.E. Polyamine catabolism and disease. Biochem. J. 2009;421(3):323–338. https://doi.org/10.1042/bj20090598Casero Jr R.A., Pegg A.E. Polyamine catabolism and disease. Biochem. J. 2009;421(3):323–338. https://doi.org/10.1042/bj20090598Seiler N., Eichentopf B. 4-Aminobutyrate in mammalian putrescine catabolism. Biochem. J. 1975;152(2):201–210. https://doi.org/10.1042/bj1520201Seiler N., Eichentopf B. 4-Aminobutyrate in mammalian putrescine catabolism. Biochem. J. 1975;152(2):201–210. https://doi.org/10.1042/bj1520201Burkard W.P., Gey K.F., Pletscher A. Diamine oxidase in the brain of vertebrates. J. Neurochem. 1963;10(3):183–186. https://doi.org/10.1111/j.1471-4159.1963.tb09481.xBurkard W.P., Gey K.F., Pletscher A. Diamine oxidase in the brain of vertebrates. J. Neurochem. 1963;10(3):183–186. https://doi.org/10.1111/j.1471-4159.1963.tb09481.xSeiler N., Schmidt-Glenewinkel T., Sarhan S. On the formation of γ-aminobutyric acid from putrescine in brain. J. Biochem. 1979;86(1):277–278.Seiler N., Schmidt-Glenewinkel T., Sarhan S. On the formation of γ-aminobutyric acid from putrescine in brain. J. Biochem. 1979;86(1):277–278.Seiler N., Lamberty U., Al‐Therib M.J. Acetyl-Coenzyme A:1, 4‐diaminobutane N‐acetyltransfetase: activity in rat brain during development, in experimental brain tumors and in brains of fish of different metabolic activity. J. Neurochem. 1975;24(4):797–800.Seiler N., Lamberty U., Al‐Therib M.J. Acetyl-Coenzyme A:1, 4‐diaminobutane N‐acetyltransfetase: activity in rat brain during development, in experimental brain tumors and in brains of fish of different metabolic activity. J. Neurochem. 1975;24(4):797–800.Seiler N., Al-Therib M.J. Acetyl-CoA:1, 4-diaminobutane N-acetyltransferase occurence in vertebrate organs and subcellular localization. Biochim. Biophys. Acta. Gen. Subj. 1974;354(2):206–212. https://doi.org/10.1016/0304-4165(74)90007-5Seiler N., Al-Therib M.J. Acetyl-CoA:1, 4-diaminobutane N-acetyltransferase occurence in vertebrate organs and subcellular localization. Biochim. Biophys. Acta. Gen. Subj. 1974;354(2):206–212. https://doi.org/10.1016/0304-4165(74)90007-5Sessa A., Perin A. Diamine oxidase in relation to diamine and polyamine metabolism. Agents and Actions. 1994;43(1–2):69–77. https://doi.org/10.1007/BF02005768Sessa A., Perin A. Diamine oxidase in relation to diamine and polyamine metabolism. Agents and Actions. 1994;43(1–2):69–77. https://doi.org/10.1007/BF02005768Missala K., Sourkes T.L., Putrescine catabolism in rats given heparin or aminoguanidine. Eur. J. Pharmacol. 1980;64(4):307–311. https://doi.org/10.1016/0014-2999(80)90238-1Missala K., Sourkes T.L., Putrescine catabolism in rats given heparin or aminoguanidine. Eur. J. Pharmacol. 1980;64(4):307–311. https://doi.org/10.1016/0014-2999(80)90238-1Schayer R.W., Smiley R.L., Kennedy J. Diamine oxidase and cadaverine metabolism. J. Biol. Chem. 1954;206(1):461–464.Schayer R.W., Smiley R.L., Kennedy J. Diamine oxidase and cadaverine metabolism. J. Biol. Chem. 1954;206(1):461–464.Ekegren T., Gomes-Trolin C., Nygren I., Askmark H. Maintained regulation of polyamines in spinal cord from patients with amyotrophic lateral sclerosis. J. Neurol. Sci. 2004;222(1–2):49–53. https://doi.org/10.1016/j.jns.2004.04.011Ekegren T., Gomes-Trolin C., Nygren I., Askmark H. Maintained regulation of polyamines in spinal cord from patients with amyotrophic lateral sclerosis. J. Neurol. Sci. 2004;222(1–2):49–53. https://doi.org/10.1016/j.jns.2004.04.011Ekegren T., Gomes-Trolin C. Determination of polyamines in human tissues by precolumn derivatization with 9-fluorenylmethyl chloroformate and high-performance liquid chromatography. Anal. Biochem. 2005;338(2):179–185. https://doi.org/10.1016/j.ab.2004.11.040Ekegren T., Gomes-Trolin C. Determination of polyamines in human tissues by precolumn derivatization with 9-fluorenylmethyl chloroformate and high-performance liquid chromatography. Anal. Biochem. 2005;338(2):179–185. https://doi.org/10.1016/j.ab.2004.11.040Wallace H.M., Fraser A.V. Inhibitors of polyamine metabolism. Amino acids. 2004;26(4):353–365. https://doi.org/10.1007/s00726-004-0092-6Wallace H.M., Fraser A.V. Inhibitors of polyamine metabolism. Amino acids. 2004;26(4):353–365. https://doi.org/10.1007/s00726-004-0092-6Palmer A.J., Wallace H.M. The polyamine transport system as a target for anticancer drug development. Amino acids. 2010;38(2):415–422. https://doi.org/10.1007/s00726-009-0400-2Palmer A.J., Wallace H.M. The polyamine transport system as a target for anticancer drug development. Amino acids. 2010;38(2):415–422. https://doi.org/10.1007/s00726-009-0400-2Bardocz S., Grant G., Brown D.S., Pusztai A. Polyamines in food―implications for growth and health. J. Nutr. Biochem. 1993;4(2):66–71. https://doi.org/10.1016/0955-2863(93)90001-DBardocz S., Grant G., Brown D.S., Pusztai A. Polyamines in food―implications for growth and health. J. Nutr. Biochem. 1993;4(2):66–71. https://doi.org/10.1016/0955-2863(93)90001-DAsk A., Persson L., Heby O. Increased survival of L1210 leukemic mice by prevention of the utilization of extracellular polyamines. Studies using a polyamineuptake mutant, antibiotics and a polyamine-deficient diet. Cancer Lett. 1992;66(1):29–34. https://doi.org/10.1016/0304-3835(92)90276-2Ask A., Persson L., Heby O. Increased survival of L1210 leukemic mice by prevention of the utilization of extracellular polyamines. Studies using a polyamineuptake mutant, antibiotics and a polyamine-deficient diet. Cancer Lett. 1992;66(1):29–34. https://doi.org/10.1016/0304-3835(92)90276-2Igarashi K., Ito K., Kashiwagi K. Polyamine uptake systems in Escherichia coli. Res. Microbiol. 2001;152(3–4):271–278. https://doi.org/10.1016/S0923-2508(01)01198-6Igarashi K., Ito K., Kashiwagi K. Polyamine uptake systems in Escherichia coli. Res. Microbiol. 2001;152(3–4):271–278. https://doi.org/10.1016/S0923-2508(01)01198-6Poulin R., Casero R.A., Soulet D. Recent advances in the molecular biology of metazoan polyamine transport. Amino acids. 2012;42(2–3):711–723. https://doi.org/10.1007/s00726-011-0987-yPoulin R., Casero R.A., Soulet D. Recent advances in the molecular biology of metazoan polyamine transport. Amino acids. 2012;42(2–3):711–723. https://doi.org/10.1007/s00726-011-0987-ySoulet D., Gagnon B., Rivest S., Audette M., Poulin R. A fluorescent probe of polyamine transport accumulates into intracellular acidic vesicles via a two-step mechanism. J. Biol. Chem. 2004;279(47):49355–49366. https://doi.org/10.1074/jbc.M401287200Soulet D., Gagnon B., Rivest S., Audette M., Poulin R. A fluorescent probe of polyamine transport accumulates into intracellular acidic vesicles via a two-step mechanism. J. Biol. Chem. 2004;279(47):49355–49366. https://doi.org/10.1074/jbc.M401287200Belting M., Mani K., Jönsson M., Cheng F., Sandgren S., Jonsson S., Ding K., Delcros J., Fransson L. Glypican-1 is a vehicle for polyamine uptake in mammalian cells a pivotal role for nitrosothiol-derived nitric oxide. J. Biol. Chem. 2003;278(47):47181–47189. https://doi.org/10.1074/jbc.M308325200Belting M., Mani K., Jönsson M., Cheng F., Sandgren S., Jonsson S., Ding K., Delcros J., Fransson L. Glypican-1 is a vehicle for polyamine uptake in mammalian cells a pivotal role for nitrosothiol-derived nitric oxide. J. Biol. Chem. 2003;278(47):47181–47189. https://doi.org/10.1074/jbc.M308325200Uemura T., Yerushalmi H.F., Tsaprailis G., Stringer D.E., Pastorian K.E., Hawel L., Byus C.V., Gerner E.W. Identification and characterization of a diamine exporter in colon epithelial cells. J. Biol. Chem. 2008;283(39):26428–26435. https://doi.org/10.1074/jbc.M804714200Uemura T., Yerushalmi H.F., Tsaprailis G., Stringer D.E., Pastorian K.E., Hawel L., Byus C.V., Gerner E.W. Identification and characterization of a diamine exporter in colon epithelial cells. J. Biol. Chem. 2008;283(39):26428–26435. https://doi.org/10.1074/jbc.M804714200Bachrach U., Seiler N. Formation of acetylpolyamines and putrescine from spermidine by normal and transformed chick embryo fibroblasts. Cancer Res. 1981;41(3):1205–1208.Bachrach U., Seiler N. Formation of acetylpolyamines and putrescine from spermidine by normal and transformed chick embryo fibroblasts. Cancer Res. 1981;41(3):1205–1208.Israel M., Rosenfield J.S., Modest E.J. Analogs of Spermine and Spermidine. I. Synthesis of Polymethylenepolyamines by Reduction of Cyanoethylated α, ι-Alkylenediamines1,2. J. Med. Chem. 1964;7(6):710–716. https://doi.org/10.1021/jm00336a006Israel M., Rosenfield J.S., Modest E.J. Analogs of Spermine and Spermidine. I. Synthesis of Polymethylenepolyamines by Reduction of Cyanoethylated α, ι-Alkylenediamines1,2. J. Med. Chem. 1964;7(6):710–716. https://doi.org/10.1021/jm00336a006Maddock C. L., D’Angio G.J., Farber S., Handler A.H. Biological studies of Actinomycin D. Ann. N. Y. Acad. Sci. 1960;89(2):386–398. https://doi.org/10.1111/j.1749-6632.1960.tb20162.xMaddock C. L., D’Angio G.J., Farber S., Handler A.H. Biological studies of Actinomycin D. Ann. N. Y. Acad. Sci. 1960;89(2):386–398. https://doi.org/10.1111/j.1749-6632.1960.tb20162.xSerre D., Erbek S., Berthet N., Ronot X., Martel-Frachet V., Thomas F. Copper(II) complexes of N3 O tripodal ligands appended with pyrene and polyamine groups: anti-proliferative and nuclease activities. J. Inorg. Biochem. 2018;179:121–134. https://doi.org/10.1016/j.jinorgbio.2017.11.006Serre D., Erbek S., Berthet N., Ronot X., Martel-Frachet V., Thomas F. Copper(II) complexes of N3 O tripodal ligands appended with pyrene and polyamine groups: anti-proliferative and nuclease activities. J. Inorg. Biochem. 2018;179:121–134. https://doi.org/10.1016/j.jinorgbio.2017.11.006Silva T.M., Andersson S., Sukumaran S.K., Marques M.P., Persson L., Oredsson S. Norspermidine and novel Pd(II) and Pt(II) polynuclear complexes of norspermidine as potential antineoplastic agents against breast cancer. PLoS One. 2013;8(2):e55651. https://doi.org/10.1371/journal.pone.0055651Silva T.M., Andersson S., Sukumaran S.K., Marques M.P., Persson L., Oredsson S. Norspermidine and novel Pd(II) and Pt(II) polynuclear complexes of norspermidine as potential antineoplastic agents against breast cancer. PLoS One. 2013;8(2):e55651. https://doi.org/10.1371/journal.pone.0055651Seiler N. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr. Drug. Targets. 2003;4(7):537–564. https://doi.org/10.2174/1389450033490885Seiler N. Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors. Curr. Drug. Targets. 2003;4(7):537–564. https://doi.org/10.2174/1389450033490885Porter C.W., Cavanaugh P.F., Stolowich N., Ganis B., Kelly E., Bergeron R.J. Biological properties of N4-and N1 , N8 -spermidine derivatives in cultured L1210 leukemia cells. Cancer Res. 1985;45(5):2050–2057.Porter C.W., Cavanaugh P.F., Stolowich N., Ganis B., Kelly E., Bergeron R.J. Biological properties of N4-and N1 , N8 -spermidine derivatives in cultured L1210 leukemia cells. Cancer Res. 1985;45(5):2050–2057.Porter C.W., Berger F.G., Pegg A.E., Ganis B., Bergeron R.J. Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1 ,N8-bis(ethyl)-spermidine. Biochem. J. 1987;242(2):433–440. https://doi.org/10.1042/bj2420433Porter C.W., Berger F.G., Pegg A.E., Ganis B., Bergeron R.J. Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1 ,N8-bis(ethyl)-spermidine. Biochem. J. 1987;242(2):433–440. https://doi.org/10.1042/bj2420433Saab N.H., West E.E., Bieszk N.C., Preuss C.V., Mank A.R., Casero Jr R.A., Woster P.M. Synthesis and evaluation of unsymmetrically substituted polyamine analogs as modulators of human spermidine/spermineN1 -acetyltransferase (SSAT) and as potential antitumor agents. J. Med. Chem. 1993;36(20):2998–3004. https://doi.org/10.1021/jm00072a020Saab N.H., West E.E., Bieszk N.C., Preuss C.V., Mank A.R., Casero Jr R.A., Woster P.M. Synthesis and evaluation of unsymmetrically substituted polyamine analogs as modulators of human spermidine/spermineN1 -acetyltransferase (SSAT) and as potential antitumor agents. J. Med. Chem. 1993;36(20):2998–3004. https://doi.org/10.1021/jm00072a020Reddy V.K., Valasinas A., Sarkar A., Basu H.S., Marton L.J., Frydman B. Conformationally restricted analogues of 1 N, 12N-bisethylspermine:synthesis and growth inhibitory effects on human tumor cell lines. J. Med. Chem. 1998;41(24):4723–4732. https://doi.org/10.1021/jm980172vReddy V.K., Valasinas A., Sarkar A., Basu H.S., Marton L.J., Frydman B. Conformationally restricted analogues of 1 N, 12N-bisethylspermine:synthesis and growth inhibitory effects on human tumor cell lines. J. Med. Chem. 1998;41(24):4723–4732. https://doi.org/10.1021/jm980172vValasinas A., Sarkar A., Reddy V.K., Marton L.J., Basu H. S., Frydman, B. Conformationally restricted analogues of 1 N, 14N-bisethylhomospermine (BE-4-4-4): synthesis and growth inhibitory effects on human prostate cancer cells. J. Med. Chem. 2001;44(3):390–403. https://doi.org/10.1021/jm000309tValasinas A., Sarkar A., Reddy V.K., Marton L.J., Basu H. S., Frydman, B. Conformationally restricted analogues of 1 N, 14N-bisethylhomospermine (BE-4-4-4): synthesis and growth inhibitory effects on human prostate cancer cells. J. Med. Chem. 2001;44(3):390–403. https://doi.org/10.1021/jm000309tZagaja G.P., Shrivastav M., Marton L.J., RinkerSchaeffer C.W., Dolan M.E., Fleig M.F. Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in vivo. Cancer Chemother. Pharmacol. 1998;41(6):505–512. https://doi.org/10.1007/s002800050774Zagaja G.P., Shrivastav M., Marton L.J., RinkerSchaeffer C.W., Dolan M.E., Fleig M.F. Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in vivo. Cancer Chemother. Pharmacol. 1998;41(6):505–512. https://doi.org/10.1007/s002800050774Bergeron R.J., Wiegand J., McManis J.S., Weimar W.R., Smith R.E., Algee S.E., Fannin T.L., Slusher M.A., Snyder P.S. Polyamine analogue antidiarrheals: a structureactivity study. J. Med. Chem. 2001;44(2):232–244. https://doi.org/10.1021/jm000277+Bergeron R.J., Wiegand J., McManis J.S., Weimar W.R., Smith R.E., Algee S.E., Fannin T.L., Slusher M.A., Snyder P.S. Polyamine analogue antidiarrheals: a structureactivity study. J. Med. Chem. 2001;44(2):232–244. https://doi.org/10.1021/jm000277+Wolff A.C., Armstrong D.K., Fetting J.H., Carducci M.K., Riley C.D., Bender J.F., Casero Jr. R.A., Davidson N.E. A Phase II study of the polyamine analog N1 ,N11-diethylnorspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer. Clin. Cancer Res. 2003;9(16):5922–5928.Wolff A.C., Armstrong D.K., Fetting J.H., Carducci M.K., Riley C.D., Bender J.F., Casero Jr. R.A., Davidson N.E. A Phase II study of the polyamine analog N1 ,N11-diethylnorspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer. Clin. Cancer Res. 2003;9(16):5922–5928.Хомутов Р.М., Денисова Г.Ф., Хомутов А.Р., Белостоцкая К.М., Шлосман Р.Б., Артамонова Е.Ю. Аминооксипропиламин – эффективный ингибитор орнитиндекарбоксилазы in vitro и in vivo. Биоорганическая химия.1985;11(11):1574–1576.Khomutov R.M., Denisova G.F., Khomutov A.R., Belostotskaya K.M., Shlosman R.B., Artamonova E.Yu. Aminooxypropylamine is an effective inhibitor of ornithine decarboxylase in vitro and in vivo. Bioorganicheskya Khimiya = Russian Journal of Bioorganic Chemistry. 1985;11(11):1574–1576 (in Russ.).Khomutov A.R., Shvetsov A.S., Vepsalainen J., Kramer D.L., Porter C.W., Hyvonen T., Keinanen T., Eloranta T.O., Khomutov R.M. New aminooxy analogs of biogenic polyamines. Russ. J. Bioorganic Chem. 1996;22(7):476–478.Khomutov A.R., Shvetsov A.S., Vepsalainen J., Kramer D.L., Porter C.W., Hyvonen T., Keinanen T., Eloranta T.O., Khomutov R.M. New aminooxy analogs of biogenic polyamines. Russ. J. Bioorganic Chem. 1996;22(7):476–478.Eloranta T.O., Khomutov A.R., Khomutov R.M., Hyvönen T. Aminooxy analogues of spermidine as inhibitors of spermine synthase and substrates of hepatic polyamine acetylating activity. J. Biochem. 1990;108(4):593–598.Eloranta T.O., Khomutov A.R., Khomutov R.M., Hyvönen T. Aminooxy analogues of spermidine as inhibitors of spermine synthase and substrates of hepatic polyamine acetylating activity. J. Biochem. 1990;108(4):593–598.Khomutov M.A., Weisell J., Hyvönen M., Keinänen T.A., Vepsäläinen J., Alhonen L., Khomutov A.R., Kochetkov S.N. Hydroxylamine derivatives for regulation of spermine and spermidine metabolism. Biochemistry (Moscow). 2013;78(13):1431–1446 https://doi.org/10.1134/S0006297913130051Khomutov M.A., Weisell J., Hyvönen M., Keinänen T.A., Vepsäläinen J., Alhonen L., Khomutov A.R., Kochetkov S.N. Hydroxylamine derivatives for regulation of spermine and spermidine metabolism. Biochemistry (Moscow). 2013;78(13):1431–1446 https://doi.org/10.1134/S0006297913130051Edwards M.L., Prakash N.J., Stemerick D.M., Sunkara S.P., Bitonti A.J., Davis G.F., Dumont J.A., Bey P. Polyamine analogs with antitumor activity. J. Med. Chem. 1990;33(5):1369–1375. https://doi.org/10.1021/jm00167a014Edwards M.L., Prakash N.J., Stemerick D.M., Sunkara S.P., Bitonti A.J., Davis G.F., Dumont J.A., Bey P. Polyamine analogs with antitumor activity. J. Med. Chem. 1990;33(5):1369–1375. https://doi.org/10.1021/jm00167a014Seiler N., Douaud F., Havouis R., LeRoch N., Renault J., Vaultier M., Moulinoux J. Dimethylsilane polyamines, a new class of potential anticancer drugs. Int. J. Oncol. 1997;11(4):835–841. https://doi.org/10.3892/ijo.11.4.835Seiler N., Douaud F., Havouis R., LeRoch N., Renault J., Vaultier M., Moulinoux J. Dimethylsilane polyamines, a new class of potential anticancer drugs. Int. J. Oncol. 1997;11(4):835–841. https://doi.org/10.3892/ijo.11.4.835Levy S. B. Antibiotic resistance—the problem intensifies. Adv. Drug Deliv. Rev. 2005;57(10):1446–1450. https://doi.org/10.1016/j.addr.2005.04.001Levy S. B. Antibiotic resistance—the problem intensifies. Adv. Drug Deliv. Rev. 2005;57(10):1446–1450. https://doi.org/10.1016/j.addr.2005.04.001Xu M., Davis R.A., Feng Y., Sykes M.L., Shelper T., Avery V.M., Camp D., Quinn R.J. Ianthelliformisamines A–C, antibacterial bromotyrosine-derived metabolites from the marine sponge Suberea ianthelliformis. J. Nat. Prod. 2012;75(5):1001–1005. https://doi.org/10.1021/np300147dXu M., Davis R.A., Feng Y., Sykes M.L., Shelper T., Avery V.M., Camp D., Quinn R.J. Ianthelliformisamines A–C, antibacterial bromotyrosine-derived metabolites from the marine sponge Suberea ianthelliformis. J. Nat. Prod. 2012;75(5):1001–1005. https://doi.org/10.1021/np300147dChoudhary A., Naughton L.M., Montánchez I., Dobson A.D., Rai D.K. Current status and future prospects of marine natural products (MNPs) as antimicrobials. Mar. Drugs. 2017;15(9):272. https://doi.org/10.3390/md15090272Choudhary A., Naughton L.M., Montánchez I., Dobson A.D., Rai D.K. Current status and future prospects of marine natural products (MNPs) as antimicrobials. Mar. Drugs. 2017;15(9):272. https://doi.org/10.3390/md15090272Khan F.A., Ahmad S., Kodipelli N., Shivange G., Anindya R. Syntheses of a library of molecules on the marine natural product ianthelliformisamines platform and their biological evaluation. Org. Biomol. Chem. 2014;12(23):3847–3865. https://doi.org/10.1039/C3OB42537AKhan F.A., Ahmad S., Kodipelli N., Shivange G., Anindya R. Syntheses of a library of molecules on the marine natural product ianthelliformisamines platform and their biological evaluation. Org. Biomol. Chem. 2014;12(23):3847–3865. https://doi.org/10.1039/C3OB42537ALi S.A., Cadelis M.M., Sue K., Blanchet M., Vidal N., Brunel J.M., Bourguet-Kondracki M., Copp B.R. 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers. Bioorg. Med. Chem. 2019;27(10):2090–2099. https://doi.org/10.1016/j.bmc.2019.04.004Li S.A., Cadelis M.M., Sue K., Blanchet M., Vidal N., Brunel J.M., Bourguet-Kondracki M., Copp B.R. 6-Bromoindolglyoxylamido derivatives as antimicrobial agents and antibiotic enhancers. Bioorg. Med. Chem. 2019;27(10):2090–2099. https://doi.org/10.1016/j.bmc.2019.04.004Borselli D., Blanchet M., Bolla J.M., Muth A., Skruber K., Phanstiel IV, O., Brunel J.M. Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram‐Negative Bacteria. ChemBioChem. 2017;18(3):276–283. https://doi.org/10.1002/cbic.201600532Borselli D., Blanchet M., Bolla J.M., Muth A., Skruber K., Phanstiel IV, O., Brunel J.M. Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram‐Negative Bacteria. ChemBioChem. 2017;18(3):276–283. https://doi.org/10.1002/cbic.201600532Balakrishna R., Wood S.J., Nguyen T.B., Miller K.A., Kumar E.S., Datta A., David S.A. Structural correlates of antibacterial and membrane-permeabilizing activities in acylpolyamines. Antimicrob. Agents Chemother. 2006;50(3):852–861. https://doi.org/10.1128/aac.50.3.852-861.2006Balakrishna R., Wood S.J., Nguyen T.B., Miller K.A., Kumar E.S., Datta A., David S.A. Structural correlates of antibacterial and membrane-permeabilizing activities in acylpolyamines. Antimicrob. Agents Chemother. 2006;50(3):852–861. https://doi.org/10.1128/aac.50.3.852-861.2006Blanchet M., Borselli D., Brunel J.M. Polyamine derivatives: a revival of an old neglected scaffold to fight resistant Gram-negative bacteria? Future. Med. Chem. 2016;8(9):963–973. https://doi.org/10.4155/fmc-2016-0011Blanchet M., Borselli D., Brunel J.M. Polyamine derivatives: a revival of an old neglected scaffold to fight resistant Gram-negative bacteria? Future. Med. Chem. 2016;8(9):963–973. https://doi.org/10.4155/fmc-2016-0011Laurence D.R., Bennett P.N. Clinical Pharmacology. Edinburgh, London, and New York: Churchill Livingstone; 1987. V. 1. 788 p.Laurence D.R., Bennett P.N. Clinical Pharmacology. Edinburgh, London, and New York: Churchill Livingstone; 1987. V. 1. 788 p.Marton L.J., Pegg A.E. Polyamines as targets for therapeutic intervention. Annu. Rev. Pharmacol. Toxicol. 1995;35(1):55–91. https://doi.org/10.1146/annurev.pa.35.040195.000415Marton L.J., Pegg A.E. Polyamines as targets for therapeutic intervention. Annu. Rev. Pharmacol. Toxicol. 1995;35(1):55–91. https://doi.org/10.1146/annurev.pa.35.040195.000415Bitonti A.J., Dumont J.A., Bush T.L., Edwards M.L., Stemerick D.M., McCann P.P., Sjoerdsma A. Bis(benzyl) polyamine analogs inhibit the growth of chloroquineresistant human malaria parasites (Plasmodium falciparum) in vitro and in combination with alphadifluoromethylornithine cure murine malaria. PNAS USA. 1989;86(2):651–655. https://doi.org/10.1073/pnas.86.2.651Bitonti A.J., Dumont J.A., Bush T.L., Edwards M.L., Stemerick D.M., McCann P.P., Sjoerdsma A. Bis(benzyl) polyamine analogs inhibit the growth of chloroquineresistant human malaria parasites (Plasmodium falciparum) in vitro and in combination with alphadifluoromethylornithine cure murine malaria. PNAS USA. 1989;86(2):651–655. https://doi.org/10.1073/pnas.86.2.651Baumann R.J., Hanson W.L., McCann P.P., Sjoerdsma A., Bitonti A.J. Suppression of both antimonysusceptible and antimony-resistant Leishmania donovani by a bis(benzyl)polyamine analog. Antimicrob. Agents Chemother. 1990;34(5):722–727. https://doi.org/10.1128/aac.34.5.722Baumann R.J., Hanson W.L., McCann P.P., Sjoerdsma A., Bitonti A.J. Suppression of both antimonysusceptible and antimony-resistant Leishmania donovani by a bis(benzyl)polyamine analog. Antimicrob. Agents Chemother. 1990;34(5):722–727. https://doi.org/10.1128/aac.34.5.722Baumann R.J., McCann P.P., Bitonti A.J. Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog. Antimicrob. Agents Chemother. 1991;35(7):1403–1407. https://doi.org/10.1128/aac.35.7.1403Baumann R.J., McCann P.P., Bitonti A.J. Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog. Antimicrob. Agents Chemother. 1991;35(7):1403–1407. https://doi.org/10.1128/aac.35.7.1403Majumder S., Kierszenbaum F. Inhibition of host cell invasion and intracellular replication of Trypanosoma cruzi by N,N’-bis(benzyl)-substituted polyamine analogs. Antimicrob. Agents Chemother. 1993;37(10):2235–2238. https://doi.org/10.1128/AAC.37.10.2235Majumder S., Kierszenbaum F. Inhibition of host cell invasion and intracellular replication of Trypanosoma cruzi by N,N’-bis(benzyl)-substituted polyamine analogs. Antimicrob. Agents Chemother. 1993;37(10):2235–2238. https://doi.org/10.1128/AAC.37.10.2235Labadie G.R., Choi S.R., Avery M.A. Diamine derivatives with antiparasitic activities. Bioorganic Med. Chem. Lett. 2004;14(3):615-619. https://doi.org/10.1016/j.bmcl.2003.11.055Labadie G.R., Choi S.R., Avery M.A. Diamine derivatives with antiparasitic activities. Bioorganic Med. Chem. Lett. 2004;14(3):615-619. https://doi.org/10.1016/j.bmcl.2003.11.055Klenke B., Barrett M.P., Brun R., Gilbert I.H. Antiplasmodial activity of a series of 1,3,5-triazine-substituted polyamines. J. Antimicrob. Chemother. 2003;52(2):290–293. https://doi.org/10.1093/jac/dkg307Klenke B., Barrett M.P., Brun R., Gilbert I.H. Antiplasmodial activity of a series of 1,3,5-triazine-substituted polyamines. J. Antimicrob. Chemother. 2003;52(2):290–293. https://doi.org/10.1093/jac/dkg307Verlinden B.K., De Beer M., Pachaiyappan B., Besaans E., Andayi W.A., Reader J., Niemand J., Biljon R., Guy K., Egan T., Woster P.M., Birkholtz L.M. Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites. Bioorg. Med. Chem. 2015;23(16):5131–5143. https://doi.org/10.1016/j.bmc.2015.01.036Verlinden B.K., De Beer M., Pachaiyappan B., Besaans E., Andayi W.A., Reader J., Niemand J., Biljon R., Guy K., Egan T., Woster P.M., Birkholtz L.M. Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites. Bioorg. Med. Chem. 2015;23(16):5131–5143. https://doi.org/10.1016/j.bmc.2015.01.036Niemand J., Burger P., Verlinden B.K., Reader J., Joubert A.M., Kaiser A., Louw A.I., Kirk K., Phanstiel IV O., Brikholtz L. Anthracene-polyamine conjugates inhibit in vitro proliferation of intraerythrocytic Plasmodium falciparum parasites. Antimicrob. Agents Chemother. 2013;57(6):2874–2877. https://doi.org/10.1128/aac.00106-13Niemand J., Burger P., Verlinden B.K., Reader J., Joubert A.M., Kaiser A., Louw A.I., Kirk K., Phanstiel IV O., Brikholtz L. Anthracene-polyamine conjugates inhibit in vitro proliferation of intraerythrocytic Plasmodium falciparum parasites. Antimicrob. Agents Chemother. 2013;57(6):2874–2877. https://doi.org/10.1128/aac.00106-13Liew L.P., Pearce A.N., Kaiser M., Copp B.R. Synthesis and in vitro and in vivo evaluation of antimalarial polyamines. Eur. J. Med. Chem. 2013;69:22–31. https://doi.org/10.1016/j.ejmech.2013.07.055Liew L.P., Pearce A.N., Kaiser M., Copp B.R. Synthesis and in vitro and in vivo evaluation of antimalarial polyamines. Eur. J. Med. Chem. 2013;69:22–31. https://doi.org/10.1016/j.ejmech.2013.07.055Wang J., Kaiser M., Copp B.R. Investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents. Mar. Drugs. 2014;12(6):3138–3160. https://doi.org/10.3390/md12063138Wang J., Kaiser M., Copp B.R. Investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents. Mar. Drugs. 2014;12(6):3138–3160. https://doi.org/10.3390/md12063138El Bissati K., Redel H., Ting L.M., Lykins J.D., McPhillie M.J., Upadhya R., Woster P.M., Yarlett N., Kim K., Weiss L.M. Novel synthetic polyamines have potent antimalarial activities in vitro and in vivo by decreasing intracellular spermidine and spermine concentrations. Front. Cell. Infect. Microbiol. 2019;9:9. https://doi.org/10.3389/fcimb.2019.00009El Bissati K., Redel H., Ting L.M., Lykins J.D., McPhillie M.J., Upadhya R., Woster P.M., Yarlett N., Kim K., Weiss L.M. Novel synthetic polyamines have potent antimalarial activities in vitro and in vivo by decreasing intracellular spermidine and spermine concentrations. Front. Cell. Infect. Microbiol. 2019;9:9. https://doi.org/10.3389/fcimb.2019.00009Eckert H., Bajorath J. Molecular similarity analysis in virtual screening: foundations, limitations and novel approaches. Drug Discov. Today. 2007;12(5–6):225–233. https://doi.org/10.1016/j.drudis.2007.01.011Eckert H., Bajorath J. Molecular similarity analysis in virtual screening: foundations, limitations and novel approaches. Drug Discov. Today. 2007;12(5–6):225–233. https://doi.org/10.1016/j.drudis.2007.01.011Huang C.J., Moczydlowski E. Cytoplasmic polyamines as permeant blockers and modulators of the voltage-gated sodium channel. Biophys. J. 2001;80(3):1262–1279. https://doi.org/10.1016/S0006-3495(01)76102-4Huang C.J., Moczydlowski E. Cytoplasmic polyamines as permeant blockers and modulators of the voltage-gated sodium channel. Biophys. J. 2001;80(3):1262–1279. https://doi.org/10.1016/S0006-3495(01)76102-4Fu L.Y., Cummins T.R., Moczydlowski E.G. Sensitivity of cloned muscle, heart and neuronal voltage-gated sodium channels to block by polyamines: a possible basis for modulation of excitability in vivo. Channels. 2012;6(1):41–49. https://doi.org/10.4161/chan.19001Fu L.Y., Cummins T.R., Moczydlowski E.G. Sensitivity of cloned muscle, heart and neuronal voltage-gated sodium channels to block by polyamines: a possible basis for modulation of excitability in vivo. Channels. 2012;6(1):41–49. https://doi.org/10.4161/chan.19001Nichols C.G., Lee S. Polyamines and potassium channels: A 25-year romance. J. Biol. Chem. 2018;293(48):18779–18788. https://doi.org/10.1074/jbc.tm118.003344Nichols C.G., Lee S. Polyamines and potassium channels: A 25-year romance. J. Biol. Chem. 2018;293(48):18779–18788. https://doi.org/10.1074/jbc.tm118.003344Мельников К.Н., Вислобоков А.И., Колпакова М.Э., Борисова В.А., Игнатов Ю.Д. Калиевые ионные каналы клеточных мембран. Обзоры по клинической фармакологии и лекарственной терапии. 2009;7(1):3–27.Melnikov K.N., Vislobokov A.I., Kolpakova M.E., Borisova V.A., Ignatov Yu.D. Potassium of ionic channels of cellular membranes. Obzory po klinicheskoy farmakologii i lekarstvennoy terapii = Reviews on clinical pharmacology and drug therapy. 2009;7(1):3–27 (in Russ.).Bergeron R.J., Wiegand J., Weimar W.R., Snyder P.S. Polyamine analogue antiarrhythmics. Pharmacol. Res. 1998;38(5):367–380. https://doi.org/10.1006/phrs.1998.0384Bergeron R.J., Wiegand J., Weimar W.R., Snyder P.S. Polyamine analogue antiarrhythmics. Pharmacol. Res. 1998;38(5):367–380. https://doi.org/10.1006/phrs.1998.0384Mokrov G.V., Likhosherstov A.M., Barchukov V.V., Stolyaruk V.N., Tsorin I.B., Vititnova M.B., Kryzhanovskii S.A., Gudasheva T.A., Seredenin S.B. Synthesis and Cardiotropic Activity of Linear Methoxyphenyltriazaalkanes. Pharm. Chem. J. 2019;53(6):500–506. https://doi.org/10.1007/s11094-019-02027-7Mokrov G.V., Likhosherstov A.M., Barchukov V.V., Stolyaruk V.N., Tsorin I.B., Vititnova M.B., Kryzhanovskii S.A., Gudasheva T.A., Seredenin S.B. Synthesis and Cardiotropic Activity of Linear Methoxyphenyltriazaalkanes. Pharm. Chem. J. 2019;53(6):500–506. https://doi.org/10.1007/s11094-019-02027-7Борисова Е.Я., Афанасьева Е.Ю., Борисова Н.Ю., Арзамасцев Е.В., Черкашин М.И. Антиаритмики нового поколения класса N-замещенных аминоамидов. Лекарственный дизайн. Микроэлементы в медицине. 2005;6(3):56–61.Borisova E.Ya., Afanas’eva E.Yu., Borisova N.Yu., Arzamastsev E.V., Cherkashin M.I. New generation antiarrhythmic remedies of the N-substituted amidoamines class. Drug design. Mikroelementy v meditsine = Trace elements in medicine (Moscow). 2005;6(3):56–61 (in Russ.).Афанасьева Е.Ю., Борисова Е.Я., Арзамасцев Е.В., Борисова Н.Ю., Черкашин М.И. Токсичность новых функционально замещенных аминов. Микроэлементы в медицине. 2005;6(3):74–77.Afanas’eva E.Yu., Borisova E.Ya., Arzamastsev E.V., Borisova N.Yu., Cherkashin M.I. Toxicity of novel functionally substituted amines. Mikroelementy v meditsine = Trace elements in medicine (Moscow). 2005;6(3):74–77 (in Russ.).Williams K., Zappia A.M., Pritchett D.B., Shen Y.M., Molinoff P.B. Sensitivity of the N-methyl-d-aspartate receptor to polyamines is controlled by NR2 subunits. Mol. Pharmacol. 1994;45(5):803–809.Williams K., Zappia A.M., Pritchett D.B., Shen Y.M., Molinoff P.B. Sensitivity of the N-methyl-d-aspartate receptor to polyamines is controlled by NR2 subunits. Mol. Pharmacol. 1994;45(5):803–809.Hansen K.B., Yi F., Perszyk R.E., Furukawa H., Wollmuth L.P., Gibb A.J., Traynelis S.F. Structure, function, and allosteric modulation of NMDA receptors. J. Gen. Physiol. 2018;150(8):1081–1105. https://doi.org/10.1085/jgp.201812032Hansen K.B., Yi F., Perszyk R.E., Furukawa H., Wollmuth L.P., Gibb A.J., Traynelis S.F. Structure, function, and allosteric modulation of NMDA receptors. J. Gen. Physiol. 2018;150(8):1081–1105. https://doi.org/10.1085/jgp.201812032Kristiansen L.V., Huerta I., Beneyto M., MeadorWoodruff J.H. NMDA receptors and schizophrenia. Curr. Opin. Pharmacol. 2007;7(1):48–55. https://doi.org/10.1016/j.coph.2006.08.013Kristiansen L.V., Huerta I., Beneyto M., MeadorWoodruff J.H. NMDA receptors and schizophrenia. Curr. Opin. Pharmacol. 2007;7(1):48–55. https://doi.org/10.1016/j.coph.2006.08.013Wang R., Reddy P.H. Role of glutamate and NMDA receptors in Alzheimer’s disease. J. Alzheimer’s Dis. 2017;57(4):1041–1048. https://doi.org/10.3233/JAD-160763Wang R., Reddy P.H. Role of glutamate and NMDA receptors in Alzheimer’s disease. J. Alzheimer’s Dis. 2017;57(4):1041–1048. https://doi.org/10.3233/JAD-160763Massey P.V., Johnson B.E., Moult P.R., Auberson Y.P., Brown M.W., Molnar E., Collingridge G.L., Bashir Z.I. Differential roles of NR2 A and NR2 B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J. Neurosci. 2004;24(36):7821–7828. https://doi.org/10.1523/jneurosci.1697-04.2004Massey P.V., Johnson B.E., Moult P.R., Auberson Y.P., Brown M.W., Molnar E., Collingridge G.L., Bashir Z.I. Differential roles of NR2 A and NR2 B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J. Neurosci. 2004;24(36):7821–7828. https://doi.org/10.1523/jneurosci.1697-04.2004Adibhatla R.M., Hatcher J.F., Sailor K., Dempsey R.J. Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Res. 2002;938(1–2):81–86. https://doi.org/10.1016/s0006-8993(02)02447-2Adibhatla R.M., Hatcher J.F., Sailor K., Dempsey R.J. Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Res. 2002;938(1–2):81–86. https://doi.org/10.1016/s0006-8993(02)02447-2Harada J., Sugimoto M. Polyamines prevent apoptotic cell death in cultured cerebellar granule neurons. Brain Res. 1997;753(2):251–259. https://doi.org/10.1016/S0006-8993(97)00011-5Harada J., Sugimoto M. Polyamines prevent apoptotic cell death in cultured cerebellar granule neurons. Brain Res. 1997;753(2):251–259. https://doi.org/10.1016/S0006-8993(97)00011-5Kish S.J., Wilson J.M., Fletcher P.J. The polyamine synthesis inhibitor α-difluoromethylornithine is neuroprotective against N-methyl-D-aspartate-induced brain damage in vivo. Eur. J. Pharmacol. 1991;209(1–2):101–103. https://doi.org/10.1016/0014-2999(91)90017-kKish S.J., Wilson J.M., Fletcher P.J. The polyamine synthesis inhibitor α-difluoromethylornithine is neuroprotective against N-methyl-D-aspartate-induced brain damage in vivo. Eur. J. Pharmacol. 1991;209(1–2):101–103. https://doi.org/10.1016/0014-2999(91)90017-kSparapani M., Dall’Olio R., Gandolfi O., Ciani E., Contestabile A. Neurotoxicity of polyamines and pharmacological neuroprotection in cultures of rat cerebellar granule cells. Exp. Neurol. 1997;148(1):157–166. https://doi.org/10.1006/exnr.1997.6627Sparapani M., Dall’Olio R., Gandolfi O., Ciani E., Contestabile A. Neurotoxicity of polyamines and pharmacological neuroprotection in cultures of rat cerebellar granule cells. Exp. Neurol. 1997;148(1):157–166. https://doi.org/10.1006/exnr.1997.6627Benveniste H., Jørgensen M.B., Diemer N.H., Hansen A.J. Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. Acta Neurol. Scand. 1988;78(6):529–536. https://doi.org/10.1111/j.1600-0404.1988.tb03697.xBenveniste H., Jørgensen M.B., Diemer N.H., Hansen A.J. Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. Acta Neurol. Scand. 1988;78(6):529–536. https://doi.org/10.1111/j.1600-0404.1988.tb03697.xChao J., Seiler N., Renault J., Kashiwagi K., Masuko T., Igarashi K., Williams K. N1 -Dansyl-Spermine and N1-(n-Octanesulfonyl)-Spermine, Novel Glutamate Receptor Antagonists: Block and Permeation of N-Methyl-D-Aspartate Receptors. Mol. Pharmacol. 1997;51(5):861–871. https://doi.org/10.1124/mol.51.5.861Chao J., Seiler N., Renault J., Kashiwagi K., Masuko T., Igarashi K., Williams K. N1 -Dansyl-Spermine and N1-(n-Octanesulfonyl)-Spermine, Novel Glutamate Receptor Antagonists: Block and Permeation of N-Methyl-D-Aspartate Receptors. Mol. Pharmacol. 1997;51(5):861–871. https://doi.org/10.1124/mol.51.5.861Seiler N., Douaud F., Renault J., Delcros J.G., Havouis R., Uriac P., Moulinoux J.P. Polyamine sulfonamides with NMDA antagonist properties are potent calmodulin antagonists and cytotoxic agents. Int. J. Biochem. Cell Biol. 1998;30(3):393–406. https://doi.org/10.1016/s1357-2725(97)00150-7Seiler N., Douaud F., Renault J., Delcros J.G., Havouis R., Uriac P., Moulinoux J.P. Polyamine sulfonamides with NMDA antagonist properties are potent calmodulin antagonists and cytotoxic agents. Int. J. Biochem. Cell Biol. 1998;30(3):393–406. https://doi.org/10.1016/s1357-2725(97)00150-7Kirby B.P., Shaw G.G. Effect of spermine and N1 -dansyl-spermine on epileptiform activity in mouse cortical slices. Eur. J. Pharmacol. 2005;524(1–3):53–59. https://doi.org/10.1016/j.ejphar.2005.09.009Kirby B.P., Shaw G.G. Effect of spermine and N1 -dansyl-spermine on epileptiform activity in mouse cortical slices. Eur. J. Pharmacol. 2005;524(1–3):53–59. https://doi.org/10.1016/j.ejphar.2005.09.009Jin L., Sugiyama H., Takigawa M., Katagiri D., Tomitori H., Nishimura K., Kaur N., Phanstiel O., Kitajima M., Takayama H., Okawara T., Williams K., Kashiwagi K., Igarashi K. Comparative studies of anthraquinone- and anthracene-tetraamines as blockers of N-methyl-D-aspartate receptors. J. Pharmacol. Exp. Ther. 2007;320(1):47–55. https://doi.org/10.1124/jpet.106.110528Jin L., Sugiyama H., Takigawa M., Katagiri D., Tomitori H., Nishimura K., Kaur N., Phanstiel O., Kitajima M., Takayama H., Okawara T., Williams K., Kashiwagi K., Igarashi K. Comparative studies of anthraquinone- and anthracene-tetraamines as blockers of N-methyl-D-aspartate receptors. J. Pharmacol. Exp. Ther. 2007;320(1):47–55. https://doi.org/10.1124/jpet.106.110528Gilad G.M., Gilad V.H. Novel polyamine derivatives as neuroprotective agents. J. Pharmacol. Exp. Ther. 1999;291(1):39–43.Gilad G.M., Gilad V.H. Novel polyamine derivatives as neuroprotective agents. J. Pharmacol. Exp. Ther. 1999;291(1):39–43.Kumamoto T., Nakajima M., Uga R., Ihayazaka N., Kashihara H., Katakawa K., Ishikawa T., Saiki R., Nishimura K., Igarashi K. Design, synthesis, and evaluation of polyaminememantine hybrids as NMDA channel blockers. Bioorg. Med. Chem. 2018;26(3):603–608. https://doi.org/10.1016/j.bmc.2017.12.021Kumamoto T., Nakajima M., Uga R., Ihayazaka N., Kashihara H., Katakawa K., Ishikawa T., Saiki R., Nishimura K., Igarashi K. Design, synthesis, and evaluation of polyaminememantine hybrids as NMDA channel blockers. Bioorg. Med. Chem. 2018;26(3):603–608. https://doi.org/10.1016/j.bmc.2017.12.021Igarashi K., Shirahata A., Pahk A.J., Kashiwagi K., Williams K. Benzyl-polyamines: Novel, Potent N-MethylD-aspartate Receptor Antagonists. J. Pharmacol. Exp. Ther. 1997;283(2):533–540.Igarashi K., Shirahata A., Pahk A.J., Kashiwagi K., Williams K. Benzyl-polyamines: Novel, Potent N-MethylD-aspartate Receptor Antagonists. J. Pharmacol. Exp. Ther. 1997;283(2):533–540.Cen J., Liu L., He L., Liu M., Wang C.J., Ji B.S. N1 -(quinolin-2-ylmethyl)butane-1,4-diamine, a polyamine analogue, attenuated injury in in vitro and in vivo models of cerebral ischemia. Int. J. Dev. Neurosci. 2012;30(7):584–595. https://doi.org/10.1016/j.ijdevneu.2012.08.008Cen J., Liu L., He L., Liu M., Wang C.J., Ji B.S. N1 -(quinolin-2-ylmethyl)butane-1,4-diamine, a polyamine analogue, attenuated injury in in vitro and in vivo models of cerebral ischemia. Int. J. Dev. Neurosci. 2012;30(7):584–595. https://doi.org/10.1016/j.ijdevneu.2012.08.008Гришин Е.В., Волкова Т.М., Арсеньев А.С., Решетова О.С., Оноприенко В.В., Магазаник Л.Г., Антонов С.М., Федорова И.М. Структурно-функциональная характеристика аргиопина – блокатора ионных каналов из яда паука Argiope lobata. Биоорганическая Химия. 1986;12(8):1121–1124. [Grishin E.V., Volkova T.M., Arseniev A.S., Reshetova O.S., Onoprienko V.V., Magazanik L.G., Antonov S.M., Fedorova I.M. Structure-functional characteristics of argiopine―an ion channel blocker from the venom of spider Argiope lobata. Bioorganicheskya Khimiya = Russian Journal of Bioorganic Chemistry. 1986;12 (8):1121–1124 (in Russ.).]Гришин Е.В., Волкова Т.М., Арсеньев А.С., Решетова О.С., Оноприенко В.В., Магазаник Л.Г., Антонов С.М., Федорова И.М. Структурно-функциональная характеристика аргиопина – блокатора ионных каналов из яда паука Argiope lobata. Биоорганическая Химия. 1986;12(8):1121–1124. [Grishin E.V., Volkova T.M., Arseniev A.S., Reshetova O.S., Onoprienko V.V., Magazanik L.G., Antonov S.M., Fedorova I.M. Structure-functional characteristics of argiopine―an ion channel blocker from the venom of spider Argiope lobata. Bioorganicheskya Khimiya = Russian Journal of Bioorganic Chemistry. 1986;12 (8):1121–1124 (in Russ.).]Nelson J.K., Frølund S.U., Tikhonov D.B., Kristensen A.S., Strømgaard K. Inside Cover: Synthesis and Biological Activity of Argiotoxin 636 and Analogues: Selective Antagonists for Ionotropic Glutamate Receptors. Angew. Chem. Int. Ed. 2009;48(17):2994–2994. https://doi.org/10.1002/anie.200990085Nelson J.K., Frølund S.U., Tikhonov D.B., Kristensen A.S., Strømgaard K. Inside Cover: Synthesis and Biological Activity of Argiotoxin 636 and Analogues: Selective Antagonists for Ionotropic Glutamate Receptors. Angew. Chem. Int. Ed. 2009;48(17):2994–2994. https://doi.org/10.1002/anie.200990085Wimo A. Pharmajmes. Res. 2003;3(6):675–680. https://doi.org/10.1586/14737167.3.6.675Wimo A. Pharmajmes. Res. 2003;3(6):675–680. https://doi.org/10.1586/14737167.3.6.675Iino M., Koike M., Isa T., Ozawa S. Voltage‐dependent blockage of Ca (2+)-permeable AMPA receptors by joro spider toxin in cultured rat hippocampal neurones. J. Physiol. 1996;496(2):431–437. https://doi.org/10.1113/jphysiol.1996.sp021696Iino M., Koike M., Isa T., Ozawa S. Voltage‐dependent blockage of Ca (2+)-permeable AMPA receptors by joro spider toxin in cultured rat hippocampal neurones. J. Physiol. 1996;496(2):431–437. https://doi.org/10.1113/jphysiol.1996.sp021696Salamoni S.D., da Costa J.C., Palma M.S., Konno K., Nihei K.I., Azambuja N.A., Neto E.P., Venturin G.T., Tavares A.A., Abreu D.S., Breda R.V. The antiepileptic activity of JSTX-3 is mediated by N-methyl-D-aspartate receptors in human hippocampal neurons. Neuroreport. 2005;16(16):1869–1873. https://doi.org/10.1097/01.wnr.0000185012.98821.2bSalamoni S.D., da Costa J.C., Palma M.S., Konno K., Nihei K.I., Azambuja N.A., Neto E.P., Venturin G.T., Tavares A.A., Abreu D.S., Breda R.V. The antiepileptic activity of JSTX-3 is mediated by N-methyl-D-aspartate receptors in human hippocampal neurons. Neuroreport. 2005;16(16):1869–1873. https://doi.org/10.1097/01.wnr.0000185012.98821.2bAndersen T.F., Vogensen S.B., Jensen L.S., Knapp K.M., Strømgaard K. Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. Bioorg. Med. Chem. 2005;13(17):5104–5112. https://doi.org/10.1016/j.bmc.2005.05.023Andersen T.F., Vogensen S.B., Jensen L.S., Knapp K.M., Strømgaard K. Design and synthesis of labeled analogs of PhTX-56, a potent and selective AMPA receptor antagonist. Bioorg. Med. Chem. 2005;13(17):5104–5112. https://doi.org/10.1016/j.bmc.2005.05.023Nurowska E, Tumiatti V, Dworakowska B. Effect of polyamines on the nicotinic ACh receptor. J. Pre-Clin. Clin. Res. 2018;12(3):73–76. https://doi.org/10.26444/jpccr/93936Nurowska E, Tumiatti V, Dworakowska B. Effect of polyamines on the nicotinic ACh receptor. J. Pre-Clin. Clin. Res. 2018;12(3):73–76. https://doi.org/10.26444/jpccr/93936Harris J., Mundey M., Tomlinson S., Mellor I., Nakanishi K., Bell D., Usherwood P.N.R. Interaction of polyamide toxin Philanthotoxin-343 with cloned and mutant glutamate receptors expressed in Xenopus oocytes. Toxicon. 1996;7(34):730–731.Harris J., Mundey M., Tomlinson S., Mellor I., Nakanishi K., Bell D., Usherwood P.N.R. Interaction of polyamide toxin Philanthotoxin-343 with cloned and mutant glutamate receptors expressed in Xenopus oocytes. Toxicon. 1996;7(34):730–731.Karst H., Piek T. Structure-activity relationship of philanthotoxins—II. Effects on the glutamate gated ion channels of the locust muscle fibre membrane. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 1991;98(2–3):479–489. https://doi.org/10.1016/0742-8413(91)90237-nKarst H., Piek T. Structure-activity relationship of philanthotoxins—II. Effects on the glutamate gated ion channels of the locust muscle fibre membrane. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 1991;98(2–3):479–489. https://doi.org/10.1016/0742-8413(91)90237-nJensen L.S., Bølcho U., Egebjerg J., Strømgaard K. Design, Synthesis, and Pharmacological Characterization of Polyamine Toxin Derivatives: Potent Ligands for the Pore‐Forming Region of AMPA Receptors. ChemMedChem. 2006;1(4):419–428. https://doi.org/10.1002/cmdc.200500093Jensen L.S., Bølcho U., Egebjerg J., Strømgaard K. Design, Synthesis, and Pharmacological Characterization of Polyamine Toxin Derivatives: Potent Ligands for the Pore‐Forming Region of AMPA Receptors. ChemMedChem. 2006;1(4):419–428. https://doi.org/10.1002/cmdc.200500093Strømgaard K., Mellor I. AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins. Med. Res. Rev. 2004;24(5):589–620. https://doi.org/10.1002/med.20004Strømgaard K., Mellor I. AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins. Med. Res. Rev. 2004;24(5):589–620. https://doi.org/10.1002/med.20004Olsen C.A., Mellor I.R., Wellendorph P., Usherwood P.N., Witt M., Franzyk H., Jaroszewski J.W. Tuning Wasp Toxin Structure for Nicotinic Receptor Antagonism: Cyclohexylalanine‐Containing Analogues as Potent and Voltage-Dependent Blockers. ChemMedChem. 2006;1(3):303–305. https://doi.org/10.1002/cmdc.200500067Olsen C.A., Mellor I.R., Wellendorph P., Usherwood P.N., Witt M., Franzyk H., Jaroszewski J.W. Tuning Wasp Toxin Structure for Nicotinic Receptor Antagonism: Cyclohexylalanine‐Containing Analogues as Potent and Voltage-Dependent Blockers. ChemMedChem. 2006;1(3):303–305. https://doi.org/10.1002/cmdc.200500067Strømgaard K., Mellor I.R., Andersen K., Neagoe I., Pluteanu F., Usherwood P.N., Krogsgaard-Larsen P., Jaroszewski J.W. Solid-Phase synthesis and pharmacological evaluation of analogues of PhTX-12—A potent and selective nicotinic acetylcholine receptor antagonist. Bioorganic Med. Chem. Lett. 2002;12(8):1159–1162. https://doi.org/10.1016/S0960-894X(02)00120-8Strømgaard K., Mellor I.R., Andersen K., Neagoe I., Pluteanu F., Usherwood P.N., Krogsgaard-Larsen P., Jaroszewski J.W. Solid-Phase synthesis and pharmacological evaluation of analogues of PhTX-12—A potent and selective nicotinic acetylcholine receptor antagonist. Bioorganic Med. Chem. Lett. 2002;12(8):1159–1162. https://doi.org/10.1016/S0960-894X(02)00120-8Bolognesi M.L., Rosini M., Andrisano V., Bartolini M., Minarini A., Tumiatti V., Melchiorre C. MTDL design strategy in the context of Alzheimer's disease: from lipocrine to memoquin and beyond. Curr. Pharm. Des. 2009;15(6):601–613. https://doi.org/10.2174/138161209787315585Bolognesi M.L., Rosini M., Andrisano V., Bartolini M., Minarini A., Tumiatti V., Melchiorre C. MTDL design strategy in the context of Alzheimer's disease: from lipocrine to memoquin and beyond. Curr. Pharm. Des. 2009;15(6):601–613. https://doi.org/10.2174/138161209787315585Kabir A., Jash C., Payghan P.V., Ghoshal N., Kumar G.S. Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation. Biochim. Biophys. Acta. Gen. Subj. 2020;1864(5):129557. https://doi.org/10.1016/j.bbagen.2020.129557Kabir A., Jash C., Payghan P.V., Ghoshal N., Kumar G.S. Polyamines and its analogue modulates amyloid fibrillation in lysozyme: A comparative investigation. Biochim. Biophys. Acta. Gen. Subj. 2020;1864(5):129557. https://doi.org/10.1016/j.bbagen.2020.129557Selkoe D.J., Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 2016;8(6):595–608. https://doi.org/10.15252/emmm.201606210Selkoe D.J., Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 2016;8(6):595–608. https://doi.org/10.15252/emmm.201606210Blennow K., Mattsson N., Schöll M., Hansson O., Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol. Sci. 2015;36(5):297–309. https://doi.org/10.1016/j.tips.2015.03.002Blennow K., Mattsson N., Schöll M., Hansson O., Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol. Sci. 2015;36(5):297–309. https://doi.org/10.1016/j.tips.2015.03.002Di Paolo M.L., Cozza G., Milelli A., Zonta F., Sarno S., Minniti E., Ursini F., Rosini M., Minarini A. Benextramine and derivatives as novel human monoamine oxidases inhibitors: an integrated approach. FEBS J. 2019;286(24):4995–5015. https://doi.org/10.1111/febs.14994Di Paolo M.L., Cozza G., Milelli A., Zonta F., Sarno S., Minniti E., Ursini F., Rosini M., Minarini A. Benextramine and derivatives as novel human monoamine oxidases inhibitors: an integrated approach. FEBS J. 2019;286(24):4995–5015. https://doi.org/10.1111/febs.14994Caslake R., Macleod A., Ives N., Stowe R., Counsell C. Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson’s disease. Cochrane Database Syst. Rev. 2009; 4. Art. No. :CD006661. https://doi.org/10.1002/14651858.cd006661.pub2Caslake R., Macleod A., Ives N., Stowe R., Counsell C. Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson’s disease. Cochrane Database Syst. Rev. 2009;4. Art. No. :CD006661. https://doi.org/10.1002/14651858.cd006661.pub2Riederer P., Müller T. Use of monoamine oxidase inhibitors in chronic neurodegeneration. Expert Opin. Drug. Metab. Toxicol. 2017;13(2):233–240. https://doi.org/10.1080/17425255.2017.1273901Riederer P., Müller T. Use of monoamine oxidase inhibitors in chronic neurodegeneration. Expert Opin. Drug. Metab. Toxicol. 2017;13(2):233–240. https://doi.org/10.1080/17425255.2017.1273901Thomas S.J., Shin M., McInnis M.G., Bostwick J.R. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment‐resistant depression. Pharmacotherapy. 2015;35(4):433–449. https://doi.org/10.1002/phar.1576Thomas S.J., Shin M., McInnis M.G., Bostwick J.R. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment‐resistant depression. Pharmacotherapy. 2015;35(4):433–449. https://doi.org/10.1002/phar.1576

The authors declare that there are no conflicts of interest present.