Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors
Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors
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DOI：
10.1016/j.bmcl.2007.09.102
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发表时间：
2007-12-01
影响因子：
2.7
通讯作者：
Neamati, Nouri
中科院分区：
文献类型：
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作者：
Al-Mawsawi, Laith Q.;Dayam, Raveendra;Neamati, Nouri
先前发现的水杨酰肼类化合物表现出有效的 HIV-1 整合酶 (IN) 抑制活性。由于纳摩尔至亚微摩尔范围内的细胞毒性，此类化合物作为抗逆转录病毒药物的开发已停止。我们利用最低限度所需的水杨酰肼子结构作为小分子数据库搜索的模板，确定了一类新型非细胞毒性酰肼 IN 抑制剂。新型酰肼表现出低微摩尔IN抑制活性，并且细胞毒性比先前公开的水杨酰肼IN抑制剂低数百倍。 (c) 2007 Elsevier Ltd. 保留所有权利。
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.