Studies of Cytotoxicity Effects, SARS‐CoV‐2 Main Protease Inhibition, and <i>in Silico</i> Interactions of Synthetic Chalcones
Octavio Lisboa Guterres Fernandes, Tiago Tizziani, Bibiana Paula Dambrós, Natália Ferreira de Sousa, Carime Lessa Mansur Pontes, Layzon Antonio Lemos da Silva, Luiz A.E. Pollo, Francisco F. de Assis, Luciana Scotti, Luciana Scotti, Antônio L. Braga, Mário Steindel, Louis P. Sandjo
Abstract
Abstract SARS‐CoV‐2 main protease (M pro ) 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 pro 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 50 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 pro (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.