Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: Docking-based CoMFA and CoMSIA analyses
Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: Docking-based CoMFA and CoMSIA analyses
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DOI：
10.1016/j.ejmech.2008.10.014
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发表时间：
2009-05-01
影响因子：
6.7
通讯作者：
Mosti, Luisa
中科院分区：
文献类型：
--
作者：
Cichero, Elena;Cesarini, Sara;Mosti, Luisa
硫代氨基甲酸酯（TCs）最近被确定为一类新的有效的非核苷类HIV-1逆转录酶（RT）抑制剂。基于分子对接研究的计算策略，以及CoMFA和CoMSIA分析，已被用于阐明RT/TC相互作用的原子细节，并确定影响TC抗逆转录病毒活性的最重要特征。CoMFA模型预测效果较好，r(2) = 0.93, r(2) = 0.53, SEE = 0.292, F = 180, r(test)(2) = 0.70。3D-QSAR场贡献与RT结合位点的结构特征表现出良好的相关性。这些研究将有助于设计具有更高效力的新型TCs，也可用于对抗临床相关的耐药突变体。(C) 2008 Elsevier Masson SAS。版权所有。
Thiocarbamates (TCs) have been recently identified as a new class of potent non-nucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses, has been used to elucidate the atomic details of the RT/TC interactions and to identify the most important features impacting the TC antiretroviral activity. The CoMFA model resulted to be the more predictive, and gave r(2) = 0.93, r(2), = 0.53, SEE = 0.292, F = 180, and r(test)(2) = 0.70. The 3D-QSAR field contributions and the structural features of the RT binding site showed a good correlation. These studies will be useful to design new TCs with improved potency also against clinically relevant resistant mutants. (C) 2008 Elsevier Masson SAS. All rights reserved.