新合成的3-苄基（苯乙基）苯并[g]喹唑啉的抗甲型肝炎病毒评估及分子对接
Anti-HAV evaluation and molecular docking of newly synthesized 3-benzyl(phenethyl)benzo[g]quinazolines.
作者信息
Al-Salahi Rashad, Anouar El Hassane, Marzouk Mohamed, Abuelizz Hatem A
机构信息
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Department of Chemistry, College of Science and Humanities, Prince Sattam bin Abdulaziz University, PO Box 83, Al Kharj 11942, Saudi Arabia.
出版信息
Bioorg Med Chem Lett. 2019 Jul 1;29(13):1614-1619. doi: 10.1016/j.bmcl.2019.04.043. Epub 2019 Apr 27.
Synthesized 3-benzyl(phenethyl)benzo[g]quinazolines (1-17) were evaluated in vitro to determine their effects against the anti-hepatitis A virus (HAV) using a cytopathic effect inhibition assay. Of the synthesized compounds, 16 and 17 showed considerably high anti-HAV activity, as indicated by their EC values of 27.59 and 18 μM, respectively, when compared to that of amantadine (37.3 μM), the standard therapeutic agent. In addition, they exhibited low cytotoxicity as indicated by their CC values, 290.63 and 569.45 μM, respectively. Compounds 1, 2, and 5 exhibited remarkable activity compared to the active compounds (16, 17) and amantadine. The selectivity index (SI) values were calculated and applied as a parameter for classifying the activity of the targets. In addition, molecular docking was performed to rationalize the SAR of the target compounds and analyze the binding modes between the docked-selected compounds and amino acid residues in the active site of the HAV-3C proteinase enzyme.
合成的3-苄基（苯乙基）苯并[g]喹唑啉类化合物（1-17）通过细胞病变效应抑制试验进行体外评估，以确定它们对甲型肝炎病毒（HAV）的作用。在所合成的化合物中，16和17显示出相当高的抗HAV活性，与标准治疗剂金刚烷胺（37.3 μM）相比，它们的EC值分别为27.59和18 μM。此外，它们的CC值分别为290.63和569.45 μM，表明细胞毒性较低。与活性化合物（16、17）和金刚烷胺相比，化合物1、2和5表现出显著活性。计算了选择性指数（SI）值，并将其作为分类目标活性的参数。此外，进行了分子对接，以合理化目标化合物的构效关系，并分析对接选择的化合物与甲型肝炎病毒3C蛋白酶活性位点中的氨基酸残基之间的结合模式。
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