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 develo** novel potent tyrosinase inhibitors.
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Sharad Kumar Suthar, and Vaibhav Aggarwal authors hold an equal contribution.
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Suthar, S.K., Aggarwal, V., Chauhan, M. et al. Molecular docking and biological evaluation of hydroxy-substituted (Z)-3-benzylideneindolin-2-one chalcones for the lead identification as tyrosinase inhibitors. Med Chem Res 24, 1331–1341 (2015). https://doi.org/10.1007/s00044-014-1225-4
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DOI: https://doi.org/10.1007/s00044-014-1225-4