Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil.
Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil.
Chem Biodivers. 2023 Mar;20(3):e202201151. doi: 10.1002/cbdv.202201151. Epub 2023 Feb 14.
SARS-CoV-2 main protease (M ) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against M of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with IC ranging from 13.76 and 36.13 μM. Except for 35 and 36, other active compounds were not cytotoxic up to 150 μM against THP-1 and Vero cell lines. Compounds 10, and 35-39 showed no hemolysis while 28 was weakly hemotoxic at 150 μM. Moreover, molecular docking showed interactions between compound 10 and M (PDBID 5RG2 and 5RG3) with proximity to cys145 and His41, suggesting a covalent binding. Products of the reaction between chalcones and cyclohexanethiol indicated that this binding could be a Michael addition type.
严重急性呼吸综合征冠状病毒 2 主蛋白酶 (M) 在促进冠状病毒复制的蛋白水解切割中发挥着重要作用。因此，减弱这种酶的活性是开发抗病毒药物的一种策略。我们报告了 40 种合成查尔酮对 M 的抑制作用，以及细胞毒性、溶血和活性化合物的计算相互作用。其中 7 种具有(E)-3-(呋喃-2-基)-1-芳基-2-丙烯-1-酮骨架(10、28 和 35-39)，其酶抑制活性的 IC 范围为 13.76 至 36.13 μM。除了 35 和 36 之外，其他活性化合物在 150 μM 时对 THP-1 和 Vero 细胞系没有细胞毒性。化合物 10 和 35-39 没有溶血，而 28 在 150 μM 时表现出较弱的溶血毒性。此外，分子对接显示化合物 10 与 M(PDBID 5RG2 和 5RG3)之间的相互作用与 cys145 和 His41 接近，表明这是一种共价结合。查尔酮与环己硫醇反应的产物表明，这种结合可能是迈克尔加成类型。
