Studies of Cytotoxicity Effects,SARS-CoV-2 Main Protease Inhibition,and in Silico Interactions of Synthetic Chalcones |
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| Authors: | Octavio L. Guterres Fernandes Tiago Tizziani Bibiana P. Dambrós Natália Ferreira de Sousa Carime L. Mansur Pontes Layzon A. L. da Silva Luiz A. Escorteganha Pollo Francisco F. de Assis Marcus T. Scotti Luciana Scotti Antonio L. Braga Mario Steindel Louis P. Sandjo |
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| Affiliation: | 1. Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900 Florianópolis, SC, Brazil;2. Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, Santa Catarina, Brazil;3. Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Universidade Federal de Paraíba, 50670-910 João Pessoa, Paraíba, Brazil;4. Postgraduate Program in Pharmacy, Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brazil |
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| Abstract: | SARS-CoV-2 main protease (Mpro) 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 Mpro 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 IC50 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 Mpro (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. |
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| Keywords: | SARS-CoV-2 Mpro inhibitory effects heterocyclic chalcones molecular docking |
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