Bioorganic Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad, 211002, India.
Department of Chemical Sciences, Indian Institute of Science Education and Research Berhampur, Odisha 760010, India.
Comput Biol Chem. 2020 Dec;89:107400. doi: 10.1016/j.compbiolchem.2020.107400. Epub 2020 Oct 6.
A series of alkylated benzimidazole derivatives was synthesized and screened for their anti-HIV, anti-YFV, and broad-spectrum antiviral properties. The physicochemical parameters and drug-like properties of the compounds were assessed first, and then docking studies and MD simulations on HIV-RT allosteric sites were conducted to find the possible mode of their action. DFT analysis was also performed to confirm the nature of the hydrogen bonding interaction of active compounds. The in silico studies indicated that the molecules behaved like possible NNRTIs. The nature - polar or non-polar and position of the substituent present at fifth, sixth, and N-1 positions of the benzimidazole moiety played an important role in determining the antiviral properties of the compounds. Among the various compounds, 2-(5,6-dibromo-2-chloro-1H-benzimidazol-1-yl)ethan-1-ol (3a) showed anti-HIV activity with an appreciably low IC value as 0.386 × 10μM. Similarly, compound 2b, 3-(2-chloro-5-nitro-1H-benzimidazol-1-yl) propan-1-ol, showed excellent inhibitory property against the yellow fever virus (YFV) with EC value as 0.7824 × 10μM.
一系列烷基化苯并咪唑衍生物被合成并筛选其抗 HIV、抗 YFV 和广谱抗病毒特性。首先评估了化合物的物理化学参数和类药性，然后对 HIV-RT 变构部位进行对接研究和 MD 模拟，以寻找其作用的可能模式。还进行了 DFT 分析以确认活性化合物氢键相互作用的性质。计算研究表明，这些分子表现出可能的 NNRTIs 特性。苯并咪唑部分的第五、第六和 N-1 位上存在的取代基的极性或非极性性质以及位置对化合物的抗病毒特性起着重要作用。在各种化合物中，2-(5,6-二溴-2-氯-1H-苯并咪唑-1-基)乙醇（3a）表现出抗 HIV 活性，IC 值相当低，为 0.386×10μM。类似地，化合物 2b，3-(2-氯-5-硝基-1H-苯并咪唑-1-基)丙-1-醇，对黄热病毒（YFV）表现出极好的抑制特性，EC 值为 0.7824×10μM。
