Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors

被引：42

作者：

Al-Mawsawi, Laith Q. ^{[1
]}

Dayam, Raveendra ^{[1
]}

Taheri, Laleh ^{[1
]}

Witvrouw, Myriam ^{[2
,3
]}

Debyser, Zeger ^{[2
,3
]}

Neamati, Nouri ^{[1
]}

机构：

[1] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Katholieke Univ Leuven, B-30006 Louvain, Belgium

[3] IRC KULAK, B-30006 Louvain, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 23期

关键词：

substructure; SAR; HIV-1; integrase; cytotoxicity;

D O I：

10.1016/j.bmcl.2007.09.102

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The previously discovered salicylhydrazide class of compounds displayed potent HIV-1 integrase ( IN) inhibitory activity. The development of this class of compounds as antiretroviral agents was halted due to cytotoxicity in the nanomolar to sub-micromolar range. We identified a novel class of non-cytotoxic hydrazide IN inhibitors utilizing the minimally required salicylhydrazide substructure as a template in a small-molecule database search. The novel hydrazides displayed low micromolar IN inhibitory activity and are several hundred-fold less cytotoxic than previously disclosed salicylhydrazide IN inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6472 / 6475

页数：4

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