Discovery, structure and HIV-1 integrase inhibitory activities of integracins, novel dimeric alkyl aromatics from Cytonaema sp.

被引：26

作者：

Singh, SB

Zink, DL

Bills, GF

Pelaez, F

Teran, A

Collado, J

Silverman, KC

Lingham, RB

Felock, P

Hazuda, DJ

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

[2] Merck Sharp & Dohme Espana, CIBE, Madrid 28027, Spain

[3] Merck Res Labs, W Point, PA 19486 USA

来源：

TETRAHEDRON LETTERS | 2002年 / 43卷 / 09期

关键词：

D O I：

10.1016/S0040-4039(02)00083-7

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Integrase is a critical viral enzyme for HIV-1 replication and is a novel target for therapeutic intervention against HIV infections. Integracins A-C are three novel dimeric alkyl aromatic inhibitors of HIV-1 integrase discovered from the screening of fungal extracts using,in in vitro assay. These compounds inhibit both coupled and strand transfer activity of HIV-1 integrase with IC50 values of 3.2-6.1 and 17-88 muM, respectively. The discovery, structure and activity of these compounds are described. (C) 2002 Published by Elsevier Science Ltd.

引用

收藏

页码：1617 / 1620

页数：4

相关论文

共 9 条

[1] HIV integrase, a brief overview from chemistry to therapeutics [J].

Craigie, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (26) :23213-23216

[2] HIV integrase structure and function [J].

Esposito, D ;

Craigie, R .

ADVANCES IN VIRUS RESEARCH, VOL 52, 1999, 52 :319-333

[3] Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells [J].

Hazuda, DJ ;

Felock, P ;

Witmer, M ;

Wolfe, A ;

Stillmock, K ;

Grobler, JA ;

Espeseth, A ;

Gabryelski, L ;

Schleif, W ;

Blau, C ;

Miller, MD .

SCIENCE, 2000, 287 (5453) :646-650

[4] Structure-based HIV-1 integrase inhibitor design: a future perspective [J].

Neamati, N .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (02) :281-296

[5] Structure and absolute stereochemistry of HIV-1 integrase inhibitor integric acid.: A novel eremophilane sesquiterpenoid produced by a Xylaria sp. [J].

Singh, SB ;

Zink, D ;

Polishook, J ;

Valentino, D ;

Shafiee, A ;

Silverman, K ;

Felock, P ;

Teran, A ;

Vilella, D ;

Hazuda, DJ ;

Lingham, RB .

TETRAHEDRON LETTERS, 1999, 40 (50) :8775-8779

[6] Equisetin and a novel opposite stereochemical homolog phomasetin, two fungal metabolites as inhibitors of HIV-1 integrase [J].

Singh, SB ;

Zink, DL ;

Goetz, MA ;

Dombrowski, AW ;

Polishook, JD ;

Hazuda, DJ .

TETRAHEDRON LETTERS, 1998, 39 (16) :2243-2246

[7] The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I [J].

Singh, SB ;

Jayasuriya, H ;

Salituro, GM ;

Zink, DL ;

Shafiee, A ;

Heimbuch, B ;

Silverman, KC ;

Lingham, RB ;

Genilloud, O ;

Teran, A ;

Vilella, D ;

Felock, P ;

Hazuda, D .

JOURNAL OF NATURAL PRODUCTS, 2001, 64 (07) :874-882

[8] Chemical and enzymatic modifications of integric acid and HIV-1 integrase inhibitory activity [J].

Singh, SB ;

Felock, P ;

Hazuda, DJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (03) :235-238

[9] 4-aryl-2,4-dioxobutanoic acid inhibitors of HIV-1 integrase and viral replication in cells [J].

Wai, JS ;

Egbertson, MS ;

Payne, LS ;

Fisher, TE ;

Embrey, MW ;

Tran, LO ;

Melamed, JY ;

Langford, HM ;

Guare, JP ;

Zhuang, LG ;

Grey, VE ;

Vacca, JP ;

Holloway, MK ;

Naylor-Olsen, AM ;

Hazuda, DJ ;

Felock, PJ ;

Wolfe, AL ;

Stillmock, KA ;

Schleif, WA ;

Gabryelski, LJ ;

Young, SD .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (26) :4923-4926