Four novel bis-(naphtho-γ-pyrones) isolated from Fusarium species as inhibitors of HIV-1 integrase

被引：44

作者：

Singh, SB

Zink, DL

Bills, GF

Teran, A

Silverman, KC

Lingham, RB

Felock, P

Hazuda, DJ

机构：

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

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(02)01057-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Integration of viral DNA into host cell DNA is an essential step in retroviral (HIV-1) replication and is catalyzed by HIV-1 integrase. HIV-1 integrase is a novel therapeutic target and is the focus of efforts to identify effective inhibitors that will prevent, or cure HIV infections, Four novel naphtho-gamma-pyrones belonging to the chaetochromin and ustilaginoidin family, were discovered as inhibitors of HIV-1 integrase from the screening Of fungal extracts using a recombinant in vitro assay. These compounds inhibit both the Coupled and strand transfer activity of HIV-1 integrase with IC50 values of 1-3 and 4-12 muM respectively. The discovery structure elucidation chemical modification and the structure-activity relationship of these compounds are described. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：713 / 717

页数：5

相关论文

共 19 条

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

Neamati, N .

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

[12] 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

[13] 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

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

Singh, SB ;

Zink, DL ;

Bills, GF ;

Pelaez, F ;

Teran, A ;

Collado, J ;

Silverman, KC ;

Lingham, RB ;

Felock, P ;

Hazuda, DJ .

TETRAHEDRON LETTERS, 2002, 43 (09) :1617-1620

[15] 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

[16] Fusidienol A: A novel Ras farnesyl-protein transferase inhibitor from Phoma sp. [J].

Singh, SB ;

Ball, RG ;

Zink, DL ;

Monaghan, RL ;

Polishook, JD ;

Sanchez, M ;

Pelaez, F ;

Silverman, KC ;

Lingham, RB .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (21) :7485-7488

[17] 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

[18] USING SIMILARITY SEARCHES OVER DATABASES OF ESTIMATED C-13 NMR-SPECTRA FOR STRUCTURE IDENTIFICATION OF NATURAL PRODUCT COMPOUNDS [J].

TSIPOURAS, A ;

ONDEYKA, J ;

DUFRESNE, C ;

LEE, S ;

SALITURO, G ;

TSOU, N ;

GOETZ, M ;

SINGH, SB ;

KEARSLEY, SK .

ANALYTICA CHIMICA ACTA, 1995, 316 (02) :161-171

[19] 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