chemicallytechFine Chemical TechnologiesТонкие химические технологии2410-65932686-7575MIREA – Russian Technological University (RTU MIREA).chemicallytech-866Research ArticleANNIVERSARIESЮБИЛЕИLipidic strategy for improving bioavailability of nucleoside HIV reverse transcriptase inhibitorЛипидная стратегия повышения биодоступности нуклеозидных ингибиторов обратной транскриптазы ВИЧШастинаН. С.ShastinaN. S.

кафедра Биотехнологии и бионанотехнологии, доцент

inosit@yandex.ruБарановаЕ. О.BaranovaE. O.

кафедра Биотехнологии и бионанотехнологии, аспирант

noemail@neicon.ruДьяковаЛ. Н.DyakovaL. N.

кафедра Биотехнологии и бионанотехнологии, аспирант

noemail@neicon.ruЛоншаковД. В.LonshakovD. V.

кафедра Биотехнологии и бионанотехнологии, студент

noemail@neicon.ruШвецВ. И.ShvetsV. I.

кафедра Биотехнологии и бионанотехнологии, заведующий кафедрой

noemail@neicon.ruМИТХТ им. М.В. Ломоносова, 119571, Москва, пр-т Вернадского, д. 86Russian Federation201128042011627180Copyright © Shastina N.S., Baranova E.O., Dyakova L.N., Lonshakov D.V., Shvets V.I., 20112011Шастина Н.С., Баранова Е.О., Дьякова Л.Н., Лоншаков Д.В., Швец В.И.Shastina N.S., Baranova E.O., Dyakova L.N., Lonshakov D.V., Shvets V.I.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/866анти-ВИЧ-нуклеозидыпролекарственные соединенияпсевдотриглицеридыинозитсодержащие фосфолипидыбиодоступностьanti-HIV-nucleosidesprodrugspseudo triglyceridesinositol containing phospholipidsbioavailabilityReferencesClercq E. Antiviral drugs in current clinical use // J. Clin. Virol. 2004. V. 30. № 2. P. 115-133.Clercq E. Antiviral drugs in current clinical use // J. Clin. Virol. 2004. V. 30. № 2. P. 115-133.Schinazi R.F., Hernandez-Santiago B.I., Hurwitz S.J. Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses // Antivir. Res. 2006. V. 71. P. 322-334.Schinazi R.F., Hernandez-Santiago B.I., Hurwitz S.J. Pharmacology of current and promising nucleosides for the treatment of human immunodeficiency viruses // Antivir. Res. 2006. V. 71. P. 322-334.Mehello Y., Clercq E. Twenty-six years of anti-HIV drug discovery: Where do we stand and where do we go? // J. Med. Chem. 2010. V. 53. P. 521-538.Mehello Y., Clercq E. Twenty-six years of anti-HIV drug discovery: Where do we stand and where do we go? // J. Med. Chem. 2010. V. 53. P. 521-538.Charman W.N., Porter C.J.H. Lipophilic prodrugs designed for intestinal lymphatic transport // Adv. Drug Deliv. Rev. 1996. V. 19. P. 149-169.Charman W.N., Porter C.J.H. Lipophilic prodrugs designed for intestinal lymphatic transport // Adv. Drug Deliv. Rev. 1996. V. 19. P. 149-169.Lambert D.M. Rationale and applications of lipids as prodrug carrier // Eur. J. Pharm. Sci. 2000. V. 11 (Suppl. 2). P. S15-S27.Lambert D.M. Rationale and applications of lipids as prodrug carrier // Eur. J. Pharm. Sci. 2000. V. 11 (Suppl. 2). P. S15-S27.Trevaskis N.L., Charman W.N., Porter C.J.H. Lipid-based delivery systems and intestinal lymphatic drug transport: A mechanistic update // Adv. Drug Deliv. Rev. 2008. V. 60. P. 702-716.Trevaskis N.L., Charman W.N., Porter C.J.H. Lipid-based delivery systems and intestinal lymphatic drug transport: A mechanistic update // Adv. Drug Deliv. Rev. 2008. V. 60. P. 702-716.Porter C.J.H., Trevaskis N.L., Charman W.N. Lipids and lipid-based formulations: Optimizing the oral delivery of lipophilic drugs // Nat. Rev. Drug Discov. 2007. V. 6. P. 231-248.Porter C.J.H., Trevaskis N.L., Charman W.N. Lipids and lipid-based formulations: Optimizing the oral delivery of lipophilic drugs // Nat. Rev. Drug Discov. 2007. V. 6. P. 231-248.Gumina G., Choi Y., Chu C.K. Antiviral nucleosides: Chiral synthesis and chemotherapy. - Amsterdam: Elsevier, 2003. P. 1-76.Gumina G., Choi Y., Chu C.K. Antiviral nucleosides: Chiral synthesis and chemotherapy. - Amsterdam: Elsevier, 2003. P. 1-76.Holy A. Antiviral acyclic nucleoside phosphonates structure activity studies // Antivir. Res. 2006. V. 71. P. 248-253.Holy A. Antiviral acyclic nucleoside phosphonates structure activity studies // Antivir. Res. 2006. V. 71. P. 248-253.Ali S.M., Khan A.R., Ahmad M.U., Sheikh S., Ahmad I. Synthesis and biological evaluation of gemcitabine-lipid conjugate (NEO6002) // Bioorg. Med. Chem. Lett. -2005. V. 15. P. 25712574.Ali S.M., Khan A.R., Ahmad M.U., Sheikh S., Ahmad I. Synthesis and biological evaluation of gemcitabine-lipid conjugate (NEO6002) // Bioorg. Med. Chem. Lett. -2005. V. 15. P. 25712574.Scriba G.K.E. Phenytoin-lipid conjugates as potential prodrugs of phenytoin // Arch. Pharm. (Weinheim). 1993. V. 326. P. 477-481.Scriba G.K.E. Phenytoin-lipid conjugates as potential prodrugs of phenytoin // Arch. Pharm. (Weinheim). 1993. V. 326. P. 477-481.Lalanne M., Paci A., Andrieux K., Dereuddre-Bosquet N., Clayette P., Deroussent A., Re M., Vassal G., Couvreur P., Desmaële D. Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV // Bioorg. Med. Chem. 2007. V. 17. P. 2237-2240.Lalanne M., Paci A., Andrieux K., Dereuddre-Bosquet N., Clayette P., Deroussent A., Re M., Vassal G., Couvreur P., Desmaële D. Synthesis and biological evaluation of two glycerolipidic prodrugs of didanosine for direct lymphatic delivery against HIV // Bioorg. Med. Chem. 2007. V. 17. P. 2237-2240.Wong A., Toth I. Lipid, sugar and liposaccharide based delivery systems // Curr. Med. Chem. 2001. V. 8. № 9. P. 1123-1136.Wong A., Toth I. Lipid, sugar and liposaccharide based delivery systems // Curr. Med. Chem. 2001. V. 8. № 9. P. 1123-1136.Clercq E. Toward improved anti-HIV chemotherapy: Therapeutic strategies for intervention with HIV infections // J. Med. Chem. 1995. V. 38. № 14. P. 2491-2517.Clercq E. Toward improved anti-HIV chemotherapy: Therapeutic strategies for intervention with HIV infections // J. Med. Chem. 1995. V. 38. № 14. P. 2491-2517.Zemlicka J. Lipophilic phosphoramidates as antiviral pronucleotides // Biochim. Biophys. Acta. 2002. V. 1587. P. 276-286.Zemlicka J. Lipophilic phosphoramidates as antiviral pronucleotides // Biochim. Biophys. Acta. 2002. V. 1587. P. 276-286.Jones R.J., Bischofberger N. Minireview: Nucleotide prodrugs // Antiviral Res. 1995. V. 27. P. 1-17.Jones R.J., Bischofberger N. Minireview: Nucleotide prodrugs // Antiviral Res. 1995. V. 27. P. 1-17.Saboulard D., Naesens L., Cahard D., Salgado A., Pathirana R., Velazquez S., McGuigan C., Clercq E., Balzarini J. Characterization of the activation pathway of phosphoramidate triester prodrugs of stavudine and zidovudine // Mol. Pharmacol. 1999. V. 56. P. 693-704.Saboulard D., Naesens L., Cahard D., Salgado A., Pathirana R., Velazquez S., McGuigan C., Clercq E., Balzarini J. Characterization of the activation pathway of phosphoramidate triester prodrugs of stavudine and zidovudine // Mol. Pharmacol. 1999. V. 56. P. 693-704.Hu L. Prodrugs: Effective solutions for solubility, permeability and targeting challenges // IDrugs. 2004. V. 7. № 8. P. 736-742.Hu L. Prodrugs: Effective solutions for solubility, permeability and targeting challenges // IDrugs. 2004. V. 7. № 8. P. 736-742.Uckun F.M., Pendergrass S., Venkatachalam T.K., Qazi S., Richman D. Stampidine is a potent inhibitor of zidovudine- and nucleoside analog reverse transcriptase inhibitor-resistant primary clinical human immunodeficiency virus type 1 isolates with thymidine analog mutations // Antimicrob. Agents Chemother. 2002. V. 46. № 11. P. 3613-3616.Uckun F.M., Pendergrass S., Venkatachalam T.K., Qazi S., Richman D. Stampidine is a potent inhibitor of zidovudine- and nucleoside analog reverse transcriptase inhibitor-resistant primary clinical human immunodeficiency virus type 1 isolates with thymidine analog mutations // Antimicrob. Agents Chemother. 2002. V. 46. № 11. P. 3613-3616.Birkus G., Hitchcock M., Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with nucleoside reverse transcriptase inhibitors // Antimicrob. Agents Chemother. 2002. V. 46. № 3. P. 716-723.Birkus G., Hitchcock M., Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with nucleoside reverse transcriptase inhibitors // Antimicrob. Agents Chemother. 2002. V. 46. № 3. P. 716-723.Clercq E. Antiviral drug discovery and development: Where chemistry meets with biomedicine // Antivir. Res. 2005. V. 67. № 2. P. 56-75.Clercq E. Antiviral drug discovery and development: Where chemistry meets with biomedicine // Antivir. Res. 2005. V. 67. № 2. P. 56-75.Schultz C. Prodrugs of biologically active phosphate esters // Bioorg. Med. Chem. 2003. V. 11. P. 885-898.Schultz C. Prodrugs of biologically active phosphate esters // Bioorg. Med. Chem. 2003. V. 11. P. 885-898.Carl P., Chakravarty P., Katzenellenbogen J. A novel connector linkage applicable in prodrug design // J. Med. Chem. 1981. V. 24. № 5. P. 479-480.Carl P., Chakravarty P., Katzenellenbogen J. A novel connector linkage applicable in prodrug design // J. Med. Chem. 1981. V. 24. № 5. P. 479-480.Schultz C., Vajanaphanich M., Harootunian A.T., Sammak J.P., Barrett E.K., Tsien Y.R. Acetoxymethyl esters of phosphates, enhancement of the permeability and potency of cAMP // J. Biol. Chem. 1993. V. 268. P. 6316-6322.Schultz C., Vajanaphanich M., Harootunian A.T., Sammak J.P., Barrett E.K., Tsien Y.R. Acetoxymethyl esters of phosphates, enhancement of the permeability and potency of cAMP // J. Biol. Chem. 1993. V. 268. P. 6316-6322.Dickson J.K., Biller S.A., Magnin D.R. [et al.]. Orally active squalene synthase inhibitors: bis((acyloxy)alkyl) prodrugs of the α-phosphonosulfonic acid moiety // J. Med. Chem. 1996. V. 39. P. 661-664.Dickson J.K., Biller S.A., Magnin D.R. [et al.]. Orally active squalene synthase inhibitors: bis((acyloxy)alkyl) prodrugs of the α-phosphonosulfonic acid moiety // J. Med. Chem. 1996. V. 39. P. 661-664.Lefebvre I., Perigaud C., Pompon A., Aubertin A.-M., Girardet J.-L., Kirn A., Gosselin G., Imbach J.-L. Mononucleoside phosphotriester derivatives with S-acyl-2-thioeyhyl bioreversible phosphate-protecting groups: Intracellular deliver of 3'-azido-2',3'-dideoxythymidine 5'-monophosphate // J. Med. Chem. 1995. V. 38. P. 3941-3950.Lefebvre I., Perigaud C., Pompon A., Aubertin A.-M., Girardet J.-L., Kirn A., Gosselin G., Imbach J.-L. Mononucleoside phosphotriester derivatives with S-acyl-2-thioeyhyl bioreversible phosphate-protecting groups: Intracellular deliver of 3'-azido-2',3'-dideoxythymidine 5'-monophosphate // J. Med. Chem. 1995. V. 38. P. 3941-3950.Villard A.-L., Coussot G., Lefebvre I., Augustijns P., Aubertin A.M., Gosselin G., Peyrottes S., Perigaud C. Phenyl phosphotriester derivatives of AZT: Variations upon the SATE moiety // Bioorg. Med. Chem. 2008. V. 16. P. 7321-7329.Villard A.-L., Coussot G., Lefebvre I., Augustijns P., Aubertin A.M., Gosselin G., Peyrottes S., Perigaud C. Phenyl phosphotriester derivatives of AZT: Variations upon the SATE moiety // Bioorg. Med. Chem. 2008. V. 16. P. 7321-7329.Meier C. cycloSal-pronucleotides - design of chemical trojan horses // Mini Rev. Med. Chem. 2002. V. 2. P. 219-234.Meier C. cycloSal-pronucleotides - design of chemical trojan horses // Mini Rev. Med. Chem. 2002. V. 2. P. 219-234.Meier C., Clercq E., Balzarini J. Nucleotide delivery from cycloSaligenyl-3'-azido-3'-deoxythymidine monophosphates (cycloSal-AZTMP) // Eur. J. Org. Chem. 1998. V. 1998. P. 837-846.Meier C., Clercq E., Balzarini J. Nucleotide delivery from cycloSaligenyl-3'-azido-3'-deoxythymidine monophosphates (cycloSal-AZTMP) // Eur. J. Org. Chem. 1998. V. 1998. P. 837-846.Meier C., Lorey M., Clercq E., Balzarini J. cycloSal-2',3'-dideoxy-2',3'-didehydrothymidine monophospate (cycloSal-d4TMP): Synthesis and antiviral evaluation of a new d4TMP delivery system // J. Med. Chem. 1998. V. 41. P. 1417-1427.Meier C., Lorey M., Clercq E., Balzarini J. cycloSal-2',3'-dideoxy-2',3'-didehydrothymidine monophospate (cycloSal-d4TMP): Synthesis and antiviral evaluation of a new d4TMP delivery system // J. Med. Chem. 1998. V. 41. P. 1417-1427.Liang Y., Narayanasamy J., Schinazib R.F., Chu C.K. Phosphoramidate and phosphate prodrugs of (-)-β-D-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies // Bioorg. Med. Chem. 2006. V. 14. P. 2178-2189.Liang Y., Narayanasamy J., Schinazib R.F., Chu C.K. Phosphoramidate and phosphate prodrugs of (-)-β-D-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies // Bioorg. Med. Chem. 2006. V. 14. P. 2178-2189.Лоншаков Д.В., Баранова Е.О., Лютик А.И., Шастина Н.С., Швец В.И. Синтез глицеролипидных производных 3'-азидо-3'-дезокситимидина и исследование их свойств // Хим.-фарм. журн. 2010. Т. 44. № 10. С. 27-34.Лоншаков Д.В., Баранова Е.О., Лютик А.И., Шастина Н.С., Швец В.И. Синтез глицеролипидных производных 3'-азидо-3'-дезокситимидина и исследование их свойств // Хим.-фарм. журн. 2010. Т. 44. № 10. С. 27-34.Berridge M.J., Lipp P., Bootman M.D. The versatility and universality of calcium signaling // Nature Rev. Mol. Cell Biol. 2000. V. 1. P. 11-21.Berridge M.J., Lipp P., Bootman M.D. The versatility and universality of calcium signaling // Nature Rev. Mol. Cell Biol. 2000. V. 1. P. 11-21.Шастина Н.С., Тучная О.А., Эйнисман Л.И., Каширичева И.И., Степанов А.Е., Юркевич А.М., Швец В.И. Исследования в области производных асимметрично замещенного мио-инозита. XXXIX. Синтез конъюгата 2`,3`-дидегидро-3`-дезокситимидина с фосфатидилинозитом, нового нуклеозидфосфолипида с потенциальной анти-ВИЧ-активностью // Биоорган. химия. 2003. Т. 29. № 3. С. 296-302.Шастина Н.С., Тучная О.А., Эйнисман Л.И., Каширичева И.И., Степанов А.Е., Юркевич А.М., Швец В.И. Исследования в области производных асимметрично замещенного мио-инозита. XXXIX. Синтез конъюгата 2`,3`-дидегидро-3`-дезокситимидина с фосфатидилинозитом, нового нуклеозидфосфолипида с потенциальной анти-ВИЧ-активностью // Биоорган. химия. 2003. Т. 29. № 3. С. 296-302.

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