Molecular Modeling of Quinoline-Based Compounds as Potential Dual Inhibitors of Reverse Transcriptase and Integrase of HIV
Molecular Modeling of Quinoline-Based Compounds as Potential Dual Inhibitors of Reverse Transcriptase and Integrase of HIV作者机构：Departamento de Farmacia Facultad de Química Universidad Nacional Autónoma de México México City México Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México Centro de Graduados e Investigación en Química del Instituto Tecnológico de Tijuana Tijuana México
出 版 物：《Computational Molecular Bioscience》 (计算分子生物学（英文）)
年 卷 期：2018年第8卷第3期
页 面：122-148页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Reverse Transcriptase Integrase Quinolone Dual Inhibitor Docking
摘 要：As follow-up of our past publication?[1], we propose that quinolones (as part of the pyridinone family) are capable to increase the number of interactions with HIV reverse transcriptase (RT) or integrase (IN) by adding a halogen in position C-8 of aromatic portion of the quinolones. This addition could help with the activity of dual inhibitors of RT and IN. In this work, we add a chlorine atom with the rationale to identify in the docking simulations a halogen interaction with the oxygen in the near aminoacids in the binding pockets of RT and IN enzymes. Our docking studies started with RT and 320 structures. Later, we took 73 structures with good results in docking with RT. The structures that we choose contain ester or acids groups in C-3 due the structural similarity with groups in charge to interact with the Mg++ ions in Elvitegravir. In conclusion, we obtained 14 structures that could occupy the allosteric pocket of RT and could inhibit the catalytic activity of IN, for this reason could be dual inhibitors. A major perspective of this work is the synthesis and testing of the potential dual inhibitors designed.
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