Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry

被引：74

作者：

Bori, Ibrahim D. ^{[1
]}

Hung, Hsin-Yi ^{[1
]}

Qian, Keduo ^{[1
]}

Chen, Chin-Ho ^{[2
]}

Morris-Natschke, Susan L. ^{[1
]}

Lee, Kuo-Hsiung ^{[1
,3
]}

机构：

[1] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

[2] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[3] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung 401, Taiwan

来源：

TETRAHEDRON LETTERS | 2012年 / 53卷 / 15期

关键词：

Betulin; Betulinic acid; AZT; Anti-HIV; Click chemistry; INHIBITOR; BEVIRIMAT; SAFETY; PHARMACOKINETICS; DERIVATIVES; MATURATION; PA-457;

D O I：

10.1016/j.tetlet.2012.02.022

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

In the present study, a new strategy to link AZT with betulin/betulinic acid (BA) by click chemistry was designed and achieved. This conjugation via a triazole linkage offers a new direction for the modification of anti-HIV triterpenes. Click chemistry provides an easy and productive way for linking two molecules, even when one of them is a large natural product. Among the newly synthesized conjugates, compounds 15 and 16 showed potent anti-HIV activity with EC50 values of 0.067 and 0.10 mu M, respectively, which are comparable to that of AZT (EC50: 0.10 mu M) in the same assay. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1987 / 1989

页数：3

共 15 条

[1] Pharmacological properties of the ubiquitous natural product betulin [J].

Alakurtti, Sami ;

Makela, Taru ;

Koskimies, Salme ;

Yli-Kauhaluoma, J. .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 29 (01) :1-13

[2]

[Anonymous], 2011, HIV AIDS STRATEGY

[3] Synthesis of triazolyl-alkylphosphonate starting from ω-azidoalkylphosphonates or ω-alkynylphosphonates [J].

Delain-Bioton, Lise ;

Villemin, Didier ;

Lohier, Jean-Francois ;

Sopkova, Jana ;

Jaffres, Paul-Alain .

TETRAHEDRON, 2007, 63 (39) :9677-9684

[4] O-Arylsulfonyl hydroxylamines via a decarboxylative rearrangement [J].

Fioravanti, Stefania ;

Pellacani, Lucio ;

Tardella, Paolo A. .

TETRAHEDRON, 2009, 65 (29-30) :5747-5751

[5] Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation [J].

Kanamoto, T ;

Kashiwada, Y ;

Kanbara, K ;

Gotoh, K ;

Yoshimori, M ;

Goto, T ;

Sano, K ;

Nakashima, H .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) :1225-1230

[6] Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents [J].

Kashiwada, Y ;

Hashimoto, F ;

Cosentino, LM ;

Chen, CH ;

Garrett, PE ;

Lee, KH .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (05) :1016-1017

[7]

Kolb HC, 2001, ANGEW CHEM INT EDIT, V40, P2004, DOI 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.3.CO

[8]

2-X

[9] PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing [J].

Li, F ;

Goila-Gaur, R ;

Salzwedel, K ;

Kilgore, NR ;

Reddick, M ;

Matallana, C ;

Castillo, A ;

Zoumplis, D ;

Martin, DE ;

Orenstein, JM ;

Allaway, GP ;

Freed, EO ;

Wild, CT .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (23) :13555-13560

[10] Safety and pharmacokinetics of bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers [J].

Martin, David E. ;

Blum, Robert ;

Wilton, John ;

Doto, Judy ;

Galbraith, Hal ;

Burgess, Gina L. ;

Smith, Philip C. ;

Ballow, Charles .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (09) :3063-3066

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