Generation of new leads as HIV-1 integrase inhibitors: 3D QSAR, docking and molecular dynamics simulation

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• 作者：Vivek K. Vyas ; Shreya Shah ; Manjunath Ghate
• 关键词：HIV ; 1 IN inhibitors ; Hydroxamic acid derivatives ; 3D QSAR ; Docking ; Molecular dynamics simulation
• 刊名：Medicinal Chemistry Research
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：26
• 期：3
• 页码：532-550
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120
• 卷排序：26

文摘

Human immunodeficiency virus type 1 integrase enzyme play a pivotal role (viral replication) in the Human immunodeficiency virus type 1 life cycle, and is recognized target for the development of anti-Human immunodeficiency virus type 1 drugs. Combination of ligand and structure-based approaches along with activity and toxicity predictions provided best lead compounds in the drug discovery process. In this study, seventy one integrase inhibitors were used for the development of 3 dimensional quantitative structure activity relationship (3D QSAR) models. The generated contour maps were used for the design of novel integrase inhibitors, and their activity and toxicity were predicted. Molecular docking study was performed to know the binding mode of designed compounds. The designed compounds showed interactions with active site amino acids, which are already proved to be important for catalysis. Molecular dynamics simulation studies of ligand-enzyme complex were carried out. Designed compound 4d was found stable in the catalytic core domain of integrase during the molecular dynamics simulations.