Molecular docking and biological evaluation of hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones for the lead identification as tyrosinase inhibitors

Abstract

The increased cases of hyperpigmentation and other related dermatological problems in human beings have led to the development of a number of tyrosinase inhibitors. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between −8.08 and −4.27 kcal/mol, while their estimated inhibition constants (Ki) were found to be between 1.20 and 736.75 µM. Among all the compounds docked, 2,4,6-trihydroxy-substituted chalcone (11) showed the lowest estimated free energy of binding followed by dihydroxy and monohydroxy-substituted analogs. In the in vitro tyrosinase inhibition assay, 11 displayed an IC50 of 46.26 µM. Moreover, in ADMET study, 11 was found to be safe and non-toxic. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones and their orientation would be useful for developing novel potent tyrosinase inhibitors.