Triterpenos como Inibidores de Fusão: Uma Nova Estratégia no Combate ao Vírus HIV

M. V. N. De Souza; R. S. B. Gonçalves; M. L. Ferreira; M. T. Ventura; M. A. Peralta

doi:10.32712/2446-4775.2006.60

Triterpenes as Fusion Inhibitors: A New Strategy Against HIV Virus

Vol. 2 No. 03 (2006)
74-81
17/10/2013
01/12/2006
https://doi.org/10.32712/2446-4775.2006.60

M. V. N. De Souza
R. S. B. Gonçalves
M. L. Ferreira
M. T. Ventura
M. A. Peralta

Keywords

Triterpenes

fusion inhibitors

virus HIV

Abstract

Acquired immunodeficiency syndrome (AIDS) is one of the most frightening diseases worldwide. Extensive effort has been spent to discover therapeutic agents targeting the etiological agent of AIDS, human immunodeficiency virus type 1 (HIV-1). Currently, the FDA (Food and Drug Administration) has approved twenty two anti-AIDS drugs including nucleoside reverse transcriptase inhibitors (zidovudine, abacavir, lamivudine, stavudine, didadosine, zalcitabine, entricitabine and tenofovir), non-nucleoside reverse transcriptase inhibitors (nevirapine, efavirenz and delavirdine), protease inhibitors (saquinavir, ritonavir, lopinavir, indinavir, nelfinavir, amprenavir, tipranavir, fosamprenavir, darunavir and atazanavir) as well fusion inhibitors (enfurvitide). This last category represents a promising strategy, due to it prevents the entrance of virus HIV in the target cell, being an important weapon in the combat to the appearance of resistant virus to medicines used. Due to the importance of alternative strategies in the fight to virus HIV and the relevance of the natural products in the discovery of new drugs, the aim of this article is to highlights triterpenes antifusing as a promising category of anti-HIV agents.

References

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betulinic acid. Journal of Medicinal Chemistry, v.45, p.4271-4275, 2002.
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Author(s)

M. V. N. De Souza
Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ
R. S. B. Gonçalves
Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ
M. L. Ferreira
Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ
M. T. Ventura
Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ
M. A. Peralta
Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fundação Oswaldo Cruz Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ

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Triterpenes as Fusion Inhibitors: A New Strategy Against HIV Virus. Rev Fitos [Internet]. 2006 Dec. 1 [cited 2024 Nov. 22];2(03):74-81. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/60

This work is licensed under a Creative Commons Attribution 4.0 International License.

[1] COHLAN, A. Trials for drug that leaves HIV defenceless. New Scientist Magazine, v.2555, n.16, 2006.

[2] DE SOUZA, M. V. N.; DE ALMEIDA, M. V. Drogas anti-HIV: Passado, presente e perspectivas futuras. Química Nova, v.26, n.3, p.366-372, 2003.

[3] DE SOUZA, M.V.N. Entry Inhibitors - A New Class of Aids Drugs. Letters in Drug Design & Discovery, v.1, p.184-193, 2004.

[4] DE SOUZA, M.V.N. Fármacos Inibidores de Fusão: uma Nova Estratégia no Combate à Replicação do Vírus VIH. Acta Farmacéutica Bonaerense, v.24, n.2, p.291-9, 2005.

[5] DE SOUZA, M.V.N. Fuzeon, o primeiro medicamento de uma nova classe anti-HIV denominada inibidores de fusão. Revista Brasileira de Farmácia, v.86, n.3, p.112-116, 2005.

[6] CRAGG, G.M.; NEWMAN, D.J.; SNADER; K.M. Natural Products in Drug Discovery and Development. The Journal of Natural Products, v.60, p.52-60, 1997.

[7] FDA: FOOD AND DRUG ADMINISTRATION. http://www.fda.gov/oashi/aids/hiv.html; Accessed in 19/12/2006.

[8] FUJIOKA, T.; KASHIWADA, Y.; KIKUSKIE, R. E.; COSENTINO, L. M.; BALLAS, L. M.; JIANG, J. B.; JANZEN, W. P.; CHEN, I. S.; LEE, K. H. The Journal of Natural Products, v.57, p.243-

[9] , 1994.

[10] GALLO, S.A.; FINNEGAN, C.M.; VIARD, M.; RAVIV, Y.; DIMITROV, A.; RAWAT, S.S.; PURI, A.;DURELL, S.; BLUMENTHAL, R. The HIV Env-mediated fusion reaction. Biochimica et Biophysica Acta, v.1614, p.36-50, 2003.

[11] HARRIES, A. D., MAHER, D., GRAHAM, S. TB/HIV: Manual Clínico, 2ª ed., WHO/HTM/TB/2004.329

[12] HARVEY, A. Strategies for discovering drugs from previously unexplored natural products. Drug Discovery Today, v.5, n.7, p. 294-300, 2000.

[13] HOLZ-SMITH, S.L.; SUN, I.C.; JIN, L.; MATTHEWS, T.J.; LEE, K.H.; CHEN, C.H. Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. Antimicrobial Agents and Chemotherapy, v. 45, n.1, p.60-66, 2001.

[14] HUANG, L.; CHEN, C. H. Molecular targets of anti-HIV-1 triterpenes. Current Drugs Targets Infection Disorders v.2, n.1, p.33-36, 2002.

[15] HUNTER, E. et. al. Sensitivity of Human Immunodeficiency Virus Type 1 to the Fusion Inhibitor T-20 Is Modulated by Coreceptor Specificity Defined by the V3 Loop of gp120. Journal of Virology, v.74, n.18, p.8358-8367, 2000.

[16] JUNG, M., KIM, H., LEE, S., KIM, H. Recent Studies on Natural Products as Anti-HIV Agents. Current Medicinal Chemistry, v.7, p.649-661, 2000.

[17] KANAMOTO, T.; KASHIWADA, Y.; KANBARA, K.; GOTOH, K.; YOSHIMORI, M.; GOTO, T.; SANO, K.; NAKASHIMA, H. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrobial Agents and Chemotherapy, v. 45, n.4, p.1225-1230, 2001.

[18] KASHIWADA, Y.; WANG, H., K.; NAGAO, T.; KITANAKA, S.; YASUDA, I.; FUJIOKA, T.; YAMAGISHI, T.; COSENTINO, M.; KOZUKA, M.; OKABE, H.; IKESHIRO, Y.; HU, C. Q.; YEH, E.; LEE, K. H. Anti-AIDS Journal of Natural Products, v.61, p.1090-1095, 1998.

[19] KASHIWADA, Y.; NAGAO, T.; HASHIMOTO, A.; IKESHIRO, Y.; OKABE, H.; COSENTINO, L. M.; LEE, K. H. Anti-AIDS Agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives. The Journal of Natural Products, v.63, p.1619-1622, 2000.

[20] LABROSSE, B.; PLESKOFF, O.; SOL, N.; JONES, C.; HENIN, Y.; ALIZON, M. Resistance to a drug blocking human immunodeficiency virus type 1 entry (RPR103611) is conferred by mutations in gp41. Journal of Virology, v.71, n.11, p.8230-8236, 1997.

[21] LABROSSE, B.; TREBOUTE, C.; ALIZON, M. sensitivity to a non-pepitidic compound (RPR103611) blocking human immunodeficiency virus type env-mediated fusion depends on sequence and accessibility of the gp41 loop region. Journal of Virology, v.74, p.2142-2150, 2000.

[22] LI, F.; GOILA-GAUR, R.; SALZWEDEL, K.; KILGORE, N.R.; REDDICK, M.; MATALLANA, C.; CASTILLO, A.; ZOUMPLIS, D.; MARTIN, D.E.; ORENSTEIN, J.M.; ALLAWAY, G.P.; FREED, E.O.; WILD, C.T. PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proceedings of the National Academy of Sciences, v.100, n.23, p.13555-13560, 2003.

[23] PEÇANHA, E.P., ANTUNES, O.A.C., TANURI, A. Estratégias farmacológicas para a terapia anti-AIDS. Quimica Nova, v. 25, n. 6B, p.1108-1116, 2002.

[24] RIMSKY, L.T.; SHUGARS, D.C.; MATHEWS, L.J. Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides, Journal of Virology, v.72, p.986-993, 1998.

[25] SINGH, I.P., BHARATE, S.B., BHUTANI, K.K.. Anti-HIV natural products. Current Science, v.89, n.2, p. 269-290, 2005.

[26] SBI: SOCIEDADE BRASILEIRA DE INFECTOLOGIA. Tratamento Hoje: Boletim Terapêutico de HIV/Aids, DST e Hepatites virais, ano I, v.3, p. 1-4, 2003.

[27] SUN, I. C.; CHEN, C. H.; KASHIWADA, Y.; WU, J. H.; WANG, H. K.; LEE, K. H. Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on

[28] betulinic acid. Journal of Medicinal Chemistry, v.45, p.4271-4275, 2002.

[29] SUN, I. C.; KASHIWADA, Y.; MORRIS-NATSCHKE, S.L.; LEE, K.H. Plant-derived terpenoids and analogues as anti-HIV agents. Current Topical in Medicinal Chemistry, v.3, n.2, p.55-169, 2003.

[30] UNESCO. Report on the global AIDS epidemic, 2006. www.fda.gov/oashi/aids/virals.html. Acesso em 18/10/06; www.who.int/hiv/en/. Acesso em 20/10/06; www.who.int/tb/hiv/faq/en/index.html. Acesso em 17/10/06.

[31] WHO: WORLD HEALTH ORGANIZATION. http://www.who.int/topics/hiv_infections/en/; Accessed in 19/12/2006.

[32] ZÃ–LLNER, B.; FEUCHAT, H.-H.; SCHRÃ–TER, M.; SCHÃ„FER, P.; PLETTENBERG, A.; STOEHR, A.; LAUFS, R. Primary genotypic resistance of HIV-1 to the fusion inhibitor T-20 in long-term infected patients. AIDS, v.15, p.935-936, 2001.