Integracides:: Tetracyclic triterpenoid inhibitors of HIV-1 integrase produced by Fusarium sp.

被引：25

作者：

Singh, SB

Zink, DL

Dombrowski, AW

Polishook, JD

Ondeyka, JG

Hirshfield, J

Felock, P

Hazuda, DJ

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 07期

关键词：

D O I：

10.1016/S0968-0896(02)00529-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

HIV-1 integrase is a critical enzyme in the replication of HIV-1. It is absent in the host cells and therefore is a good target for treatment of HIV-1 infections. Integracides are members of the tetracyclic triterpenoids family that were isolated from the fermentation broth of a Fusarium sp. Integracide A, a sulfated ester, exhibited significant inhibitory activity against strand transfer reaction of HIV-1 integrase. The discovery, structure elucidation including single crystal X-ray structure and HIV-1 inhibitory activity of these compounds are described. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1577 / 1582

页数：6

相关论文

共 22 条

[1]

Ashe B. M., 1989, [No title captured], Patent No. [US 4874755, 4874755]

[2] Novel triterpene sulfates from Fusarium compactum using a rhinovirus 3C protease inhibitor screen [J].

Brill, GM ;

Kati, WM ;

Montgomery, D ;

Karwowski, JP ;

Humphrey, PE ;

Jackson, M ;

Clement, JJ ;

Kadam, S ;

Chen, RH ;

McAlpine, JB .

JOURNAL OF ANTIBIOTICS, 1996, 49 (06) :541-546

[3]

BURG RW, 1989, Patent No. 4871727

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

Craigie, R .

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

[5] Production of a family of kinase-inhibiting lactones from fungal fermentations [J].

Dombrowski, A ;

Jenkins, R ;

Raghoobar, S ;

Bills, G ;

Polishook, J ;

Peláez, F ;

Burgess, B ;

Zhao, A ;

Huang, LY ;

Zhang, Y ;

Goetz, M .

JOURNAL OF ANTIBIOTICS, 1999, 52 (12) :1077-1085

[6] L-696,474, A NOVEL CYTOCHALASIN AS AN INHIBITOR OF HIV-1 PROTEASE .1. THE PRODUCING ORGANISM AND ITS FERMENTATION [J].

DOMBROWSKI, AW ;

BILLS, GF ;

SABNIS, G ;

KOUPAL, LR ;

MEYER, R ;

ONDEYKA, JG ;

GIACOBBE, RA ;

MONAGHAN, RL ;

LINGHAM, RB .

JOURNAL OF ANTIBIOTICS, 1992, 45 (05) :671-678

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

Esposito, D ;

Craigie, R .

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

[8] Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites [J].

Hazuda, D ;

Blau, CU ;

Felock, P ;

Hastings, J ;

Pramanik, B ;

Wolfe, A ;

Bushman, F ;

Farnet, C ;

Goetz, M ;

Williams, M ;

Silverman, K ;

Lingham, R ;

Singh, S .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1999, 10 (02) :63-70

[9] 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

[10] Cyclodidemniserinol trisulfate, a sulfated serinolipid from the Palauan ascidian Didemnum guttatum that inhibits HIV-1 integrase [J].

Mitchell, SS ;

Rhodes, D ;

Bushman, FD ;

Faulkner, DJ .

ORGANIC LETTERS, 2000, 2 (11) :1605-1607