Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: Docking-based CoMFA and CoMSIA analyses

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• 作者：Elena Cichero ; Sara Cesarini ; Paola Fossa ; Andrea Spallarossa ; Luisa Mosti
• 关键词：HIV-1 ; Reverse transcriptase ; 3D-QSAR ; CoMFA ; CoMSIA ; Thiocarbamates
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：44
• 期：5
• 页码：2059-2070
• 全文大小：2573 K

文摘

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 r² = 0.93, r_cv² = 0.53, SEE = 0.292, F = 180, and r_test² = 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.