BETULENOL DERIVATIVES AS POTENTIAL ANTI-HIV AGENTS



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

In this review, the important advances in the study of anti-HIV activity of betulenol, its natural and semisynthetic analogues obtained since 1993 are described. The perspective structures with potent anti-HIV activity are demonstrated. The structure-activity relationships of the obtained compounds are discussed. The latest trends in the development of anti-HIV agents based on the chemical modification of betulenol are underlined. The mechanisms of action of the most important agents are summarized in the review. Betulenol derivatives should be considered as a new effective class of specific inhibitors of HIV.

Full Text

Restricted Access

References

  1. Buss A. D., Butler M. S. Natural Product Chemistry for Drug Discovery (RSC Biomolecular Sciences). — Cambridge (UK): The Royal Society of Chemistry, 2010. — 458 p.
  2. Абышев А. З., Абышев Р. А., Гадзиковский С. В. и др. Противовирусная активность соединений кумаринового ряда (Часть 1) // Вич-инфекция и иммуносупрессии. — 2013. — Т. 5, № 1. — С. 34—41.
  3. Dzubak P., Hajduch M., Vydra D. et al. Pharmacological activities of natural triterpenoids and their therapeutic implications // Nat. Prod. Rep. — 2006. — Vol. 23, № 3. — P. 394-411.
  4. Jager S., Trojan H., Kopp T. et al. Pentacyclic triterpene distribution in various plants — rich sources for a new group of multi-potent plant extracts // Molecules. — 2009. — Vol. 14, № 6. — P. 2016-2031.
  5. Kuo R. Y., Qian K., Morris-Natschke S. L. et al. Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents // Nat. Prod. Rep. — 2009. — Vol. 26, № 10. — P. 1321-1344.
  6. Sun I. C., Kashiwada Y., Morris-Natschke S. L. et al. Plant-derived terpenoids and analogues as anti-HIV agents // Curr. Top Med. Chem. — 2003. — Vol. 3, № 2. — P. 155-169.
  7. Dereu N., Evers M., Soler F. et al. Structure — activity relationships of novel triterpene derivatives: a new class of potent anti-HIV 1 agents with an original mode of action // IXth International Conference on AIDS. — Berlin, 1993. — abstract № P0-A13-0568. — P. 229.
  8. Mayaux J. F., Bousseau A., Pauwels R. et al. Biological activity and novel mechanism of original triterpene derivatives, a new class of potent anti-HIV1 agents // IXth International Conference on AIDS, 1993. — abstract № WS- A17-3. — P. 33.
  9. Mayaux J. F., Bousseau A., Pauwels R. et al. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells // Proc Natl Acad Sci USA. — 1994. — Vol. 91, № 9. — P. 3564-3568.
  10. Fujioka T., Kashiwada Y., Kilkuskie R. E. et al. Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids // J. Nat Prod. — 1994. — Vol. 57, № 2. — P. 243-247.
  11. Cichewicz R. H., Kouzi S. A. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection // Medicinal Research Reviews. — 2004. — Vol. 24, № 1. — P. 90-114.
  12. Mukherjee R., Kumar V., Srivastava S. K. et al. Betulinic acid derivatives as anticancer agents: structure activity relationship // Anticancer Agents Med. Chem. — 2006. — Vol. 6, № 3. — P. 271-279.
  13. Yli-Kauhaluoma J., Alakurtti S., Vuorela P. et al. Betulin derived compounds useful as antiviral agents // Finnish Patent № W0/2007/141390, 2007.
  14. Yli-Kauhaluoma J., Alakurtti S., Minkkinen J. et al. Betulin derived compounds useful as antiprotozoal agents // US Patent Application № 2010190795A1, 2010.
  15. Yi J. E., Obminska-Mrukowicz B., Yuan L. Y. et al. Immunomodulatory effects of betulinic acid from the bark of white birch on mice // J. Vet. Sci. — 2010. — Vol. 11, № 4. — P. 305-313.
  16. Alakurtti S., Bergstrom P., Sacerdoti-Sierra N. et al. Anti-leishmanial activity of betulin derivatives // J. Antibiot (Tokyo). — 2010. — Vol. 63, № 3. — P. 123-126.
  17. Saxena B. B., Rathnam P. Betulinol derivatives as anti-hiv agents // US Patent № 8008280, 2011.
  18. Saxena B. B., Rathnam P. Betulinol derivatives as anti-cancer agents // US Patent № 8088757, 2012.
  19. Krasutsky P. A. Birch bark research and development // Nat. Prod. Rep. — 2006. — Vol. 23, № 6. — P. 919-942.
  20. Sarek J., Svoboda M., Hajduch M. Method of preparation and isolation of betulin diacetate from birch bark from paper mills and its optical processing to betulin // US Patent № 8093413B2, 2012.
  21. Абышев А. З., Агаев Э. М., Гусейнов А. Б. Исследование химического состава экстракта коры березы Cortex betula сем. Betulaceae // Химико-фармацевтический журнал. — 2007. — Т. 41, № 8. — С. 22-26.
  22. Когай Т. И., Кузнецов Б. Н. Способ получения бетулиновой кислоты // Патент РФ № 2305106, Бюл. № 24, 27.08.2007.
  23. Курбатов Е. С., Коструб В. В., Курбатов С. В. Синтез производных бетулонового альдегида // Химия растительного сырья. — 2011. — № 3. — С. 81-83.
  24. Melnikova N., Burlova I., Kiseleva T. et al. A practical synthesis of betulonic acid using selective oxidation of betulin on aluminium solid support // Molecules. — 2012. — Vol. 17, № 10. — P. 11849-11863.
  25. Dehaen W., Mashentseva A. A., Seitembetov T. S. Allobetulin and its derivatives: synthesis and biological activity // Molecules. — 2011. — Vol. 16, № 3. — P. 2443-2466.
  26. Martin D. E., Blum R., Wilton J. et al. Safety and pharmacokinetics of Bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers // Antimicrob Agents Chemother. — 2007. — Vol. 51, № 9. — P. 3063-3066.
  27. Safety and efficacy study of MPC-4326 for treatment of patients with HIV-1 infection, 2010. [http://clinicaltrials.gov/ct2/show/NCT00967187].
  28. A phase 2 study to assess the pharmacokinetics of bevirimat 100 mg tablets given to HIV-1 positive patient for 15 days, 2010 [http://clinicaltrials.gov/ct2/show/NCT01097070].
  29. Qian K., Kuo R. Y., Chen C. H. et al. Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors // J. Med. Chem. — 2010. — Vol. 53. — № 8. — P. 3133-3141.
  30. Nguyen A. T. F., Jackson C. L., Nitz K. W. et al. The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles // Retrovirology. — 2011. — Vol. 8, № 1. — P. 101.
  31. Adamson C. S., Waki K., Ablan S. D. et al. Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (PA-457) // J. Virol. — 2009. — Vol. 83, № 10. — P. 4884-4894.
  32. Van Baelen K., Salzwedel K., Rondelez E. et al. Susceptibility of human immunodeficiency virus type 1 to the maturation inhibitor bevirimat is modulated by baseline polymorphisms in Gag spacer peptide 1 // Antimicrob Agents Chemother. — 2009. — Vol. 53, № 5. — P. 2185-2188.
  33. Waki K., Durell S. R., Soheilian F. et al. Structural and functional insights into the HIV-1 maturation inhibitor binding pocket // PLoS Pathog. — 2012. — Vol. 8, № 11. — P. e1002997.
  34. Lu W., Salzwedel K., Wang D. et al. A single polymorphism in HIV-1 subtype C SP1 is sufficient to confer natural resistance to the maturation inhibitor bevirimat // Antimicrob Agents Chemother. — 2011. — Vol. 55, № 7. — P. 3324-3329.
  35. Yu D., Morris-Natschke S. L., Lee K. H. New developments in natural products-based anti-AIDS research // Med. Res Rev. — 2007. — Vol. 27, № 1. — P. 108-132.
  36. Yu D., Lee K-H. 9. Recent progress and prospects on plant-derived anti-HIV agents and analogs // Medicinal Chemistry of Bioactive Natural Products. — New Jersey (Canada): John Wiley & Sons, Inc., 2006. — Р. 357-397.
  37. Chen C. H., Huang L., Lee K.-H. Betulinic acid derivatives as anti-hiv agents // US Patent № 2011152229A1, 2011.
  38. Aiken C., Chen C. H. Betulinic acid derivatives as HIV-1 antivirals // Trends Mol Med. — 2005. — Vol. 11, № 1. — P. 31-36.
  39. Yogeeswari P., Sriram D. Betulinic acid and its derivatives: a review on their biological properties // Curr Med. Chem. — 2005. — Vol. 12, № 6. — P. 657-666.
  40. Толстиков Г. А., Флехтер О. Б., Шульц Э. Э. и др. Бетулин и его производные. Химия и биологическая активность // Химия в интересах устойчивого развития. — 2005. — Т. 13, № 1. — С. 1-30.
  41. Baglin I., Mitaine-Offer A. C., Nour M. et al. A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents // Mini Rev Med. Chem. — 2003. — Vol. 3, № 6. — P. 525-539.
  42. Cassels B., Asencio M. Anti-HIV activity of natural triterpenoids and hemisynthetic derivatives 2004-2009. Phytochemistry Reviews.— 2011. — Vol. 10, № 4. — P. 545-564.
  43. Kashiwada Y., Hashimoto F., Cosentino L. M. et al. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents // J. Med. Chem. — 1996. — Vol. 39, № 5. — P. 1016-1017.
  44. Soler F., Poujade C., Evers M. et al. Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry // J. Med. Chem 1996. — Vol. 39, № 5. — P. 1069-1083.
  45. Evers M., Poujade C., Soler F. et al. Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action // J. Med. Chem. — 1996. — Vol. 39, № 5. — P. 1056-1068.
  46. Hashimoto F., Kashiwada Y., Cosentino L. M. et al. Anti-AIDS agents XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydro-betulinic acid derivatives // Bioorg Med. Chem. — 1997. — Vol. 5, № 12. — P. 2133-2143.
  47. Sun I. C., Shen J. K., Wang H. K. et al. Anti-AIDS agents. 32. Synthesis and anti-HIV activity of betulin derivatives // Bioorg Med. Chem Lett. — 1998. — Vol. 8, № 10. — P. 1267-1272.
  48. Sun I. C., Wang H. K., Kashiwada Y. et al. Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as antiHIV agents // J. Med. Chem. — 1998. — Vol. 41, № 23. — P. 4648-4657.
  49. Kashiwada Y., Chiyo J., Ikeshiro Y. et al. Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives // Chem Pharm Bull (Tokyo). — 2000. — Vol. 48. — № 9. — P. 1387-1390.
  50. Kashiwada Y., Nagao T., Hashimoto A. et al. Anti-AIDS agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives // J. Nat Prod.— 2000.— Vol. 63, № 12. — P. 1619-1622.
  51. Kashiwada Y., Chiyo J., Ikeshiro Y. et al. 3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents. Bioorg Med. Chem Lett.— 2001.— Vol. 11, № 2. — P. 183-185.
  52. Флехтер О. Б., Карачурина Л. Т., Плясунова О. А. и др. 3,28-ди-О-никотинат бетулина, проявляющий гепатопротекторную и анти-ВИЧ активность // Патент РФ № 2174982, 2001.
  53. Sun I. C., Chen C. H., Kashiwada Y. et al. Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid // J. Med. Chem. — 2002. — Vol. 45, № 19. — P. 4271-4275.
  54. Kashiwada Y., Sekiya M., Ikeshiro Y. et al. 3-O-Glutaryl-dihydrobetulin and related monoacyl derivatives as potent anti-HIV agents // Bioorganic & Medicinal Chemistry Letters. — 2004. — Vol. 14, № 23. — P. 5851-5853.
  55. Huang L., Yuan X., Aiken C. et al. Bifunctional anti-human immunodeficiency virus type 1 small molecules with two novel mechanisms of action // Antimicrob Agents Chemother. — 2004. — Vol. 48, № 2. — P. 663-665.
  56. Phase 2 Safety and Efficacy Study of Bevirimat functional monotherapy in HIV treatment-experienced patients for 2 weeks (http://clinicaltrials. gov, Study ID: NCT00511368).
  57. Huang L., Ho P., Lee K. H. et al. Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives // Bioorg Med. Chem. — 2006. — Vol. 14, № 7. — P. 2279-2289.
  58. Huang L., Yu D., Ho P. et al. Synthesis and Anti-HIV Activity of bi-functional triterpene derivatives // Letters in Drug Design Discovery. — 2007. — Vol. 4, № 7. — P. 471-478.
  59. Gerrish D., Kim I. C., Kumar D. V. et al. Triterpene based compounds with potent anti-maturation activity against HIV-1 // Bioorg Med. Chem Lett. — 2008. — Vol. 18, № 24. — P. 6377-80.
  60. Qian K., Yu D., Chen C. H. et al. Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents // J. Med. Chem. — 2009. — Vol. 52, № 10. — P. 3248-3258.
  61. Qian K., Nakagawa-Goto K., Yu D. et al. Anti-AIDS agents 73: structure-activity relationship study and asymmetric synthesis of 3-O-monomethylsuccinyl-betulinic acid derivatives // Bioorg Med. Chem Lett. — 2007. — Vol. 17, № 23. — P. 6553-6557.
  62. Dang Z., Ho P., Zhu L. et al. New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1 // J. Med. Chem. — 2013. — Vol. 56, № 5. — P. 2029-2037.
  63. Xiong J., Kashiwada Y., Chen C.-H. et al. Conjugates of betulin derivatives with AZT as potent anti-HIV agents // Bioorganic & Medicinal Chemistry 2010. — Vol. 18, № 17. — P. 6451-6469.
  64. Bori I. D., Hung H. Y., Qian K. et al. Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry // Tetrahedron Lett. — 2012. — Vol. 53, № 15. — P. 1987-1989.
  65. Martin D. E., Power M. D. Pharmaceutical salts of 3-O-(3,3 -dimethylsuccinyl)betulinic acid // US Patent Application № 20120214775, 2012.
  66. Zhao H., Holmes S. S., Baker G. A. et al. Ionic derivatives of betulinic acid as novel HIV-1 protease inhibitors // Journal of Enzyme Inhibition and Medicinal Chemistry. — 2012. — Vol. 27, № 5. — P. 715-721.
  67. Dang Z., Lai W., Qian K. et al. Betulinic acid derivatives as human immunodeficiency virus type 2 (HIV-2) inhibitors // J. Med. Chem. — 2009. — Vol. 52, № 23. — P. 7887-7891.
  68. Reutrakul V., Anantachoke N., Pohmakotr M. et al. Anti-HIV-1 and anti-inflammatory lupanes from the leaves, twigs, and resin of Garcinia han-buryi // Planta Med. — 2010. — Vol. 76, № 4. — P. 368-371.
  69. Ma C., Nakamura N., Miyashiro H. et al. Inhibitory effects of constituents from Cynomorium songaricum and related triterpene derivatives on HIV-1 protease // Chem. Pharm. Bull. (Tokyo). — 1999. — Vol. 47, № 2. — P. 141-145.
  70. Regueiro-Ren A., Liu Z., Swidorski J. et al. С-28 amides of modified С-3 betulinic acid derivatives as HIV maturation inhibitors // US Patent Application № 20120142653, 2012.
  71. Regueiro-Ren A., Liu Z., Swidorski J. et al. С-17 and С-3 modified triterpenoids with HIV maturation inhibitory activity // US Patent Application № US20130035318, 2013.
  72. Mullauer F. B., Kessler J. H., Medema J. P. Betulinic acid, a natural compound with potent anticancer effects // Anticancer Drugs. — 2010. — Vol. 21, №3. — P. 215-227.
  73. Mukherjee R., Kumar V., Srivastava S. K. et al. Betulinic acid derivatives as anticancer agents: structure activity relationship // Anticancer Agents Med. Chem. — 2006. — Vol. 6, № 3. — P. 271-279.
  74. Udeani G. O., Zhao G. M., Geun Shin Y. et al. Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice // Biopharm. Drug Dispos. — 1999. — Vol. 20, № 8. — P. 379-383.
  75. Eiznhamer D. A., Xu Z. Q. Betulinic acid: a promising anticancer candidate // Drugs.— 2004.— Vol. 7, № 4. — P. 359-373.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2013 Abyshev A.Z., Abyshev R.A., Nguyen V.H., Morozova V.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies