Compound 6f(Mansoura University)

The current study aims at developing non-peptidic new antiviral hits against main protease (M^pro) of SARS-COV2 using the non-peptidic M^pro inhibitor tipranavir (TPV) as a starting point. In vitro protease inhibition assay of the targeted compounds indicated that compound 6f and its cyclized triazole analogue 7f were the most active in the present study with IC₅₀ values of 6.48 and 7.38 μM, respectively. These values were better than the 9.06 μM IC₅₀ value of reference standard; TPV. In general, acylthiosemicarbazide derivatives 6e-g were more potent than corresponding acylsemicarbazide derivatives 6a-c. Also, the 4-chlorophenyl combined with either thiosemicabazide or 5-mercaptotriazolyl moieties in the molecules were the best for protease inhibitory activity. Cytotoxicity testing assay suggested that the tested molecules were relatively safe for the normal human lung fibroblast cell line WI-38 with IC₅₀ values that ranged from 48.75 to 399.96 μM. Results of the molecular modeling study were consistent with those of in vitro biological evaluation. Collectively, compounds 6f and 7f could be considered as non-peptidic new antiviral hits with protease inhibitory activity for further modifications and development to potent antiviral agents as protease inhibitors.