INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS INTEGRASE BY BIS-CATECHOLS

被引：78

作者：

LAFEMINA, RL ^{[1
]}

GRAHAM, PL ^{[1
]}

LEGROW, K ^{[1
]}

HASTINGS, JC ^{[1
]}

WOLFE, A ^{[1
]}

YOUNG, SD ^{[1
]}

EMINI, EA ^{[1
]}

HAZUDA, DJ ^{[1
]}

机构：

[1] MERCK SHARP & DOHME LTD, RES LABS, DEPT MED CHEM, W POINT, PA 19486 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 1995年 / 39卷 / 02期

关键词：

D O I：

10.1128/AAC.39.2.320

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The human immunodeficiency virus type 1 (HIV-1) integrase protein is required for the productive infection of T-lymphoid cells in culture (R. L. LaFemina, C. L. Schneider, H. L. Robbins, P. L. Callahan, K. LeGrow, E. Roth, W. A. Schleif, and E. A. Emini, J. Virol, 66:7414-7419, 1992). This observation suggests that chemical inhibitors of integrase ay prevent the spread of HIV in infected individuals. In our search for such potential chemotherapeutic agents, we observed that beta-conidendrol inhibits both the sequence-dependent and sequence-independent endonucleolytic activities of integrase with comparable potencies in vitro (50% inhibitory concentration, 500 nM), Structurally related compounds tested for their abilities to inhibit integrase generated a limited structure-activity analysis which demonstrated that potency is associated with the bis-catechol structure: two pairs of adjacent hydroxyls on separate benzene rings. beta-Conidendrol did not inhibit several other endonucleases and/or phosphoryltransferases. Although beta-conidendrol was not effective in preventing HIV-1 infection in cell culture, the in vitro data demonstrate that it is possible to identify selective agents targeted against this essential HIV-1 function.

引用

页码：320 / 324

页数：5

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