Synthesis, molecular docking studies of coumarinyl-pyrazolinyl substituted thiazoles as non-competitive inhibitors of mushroom tyrosinase

A series of coumarinyl-pyrazolinyl substituted thiazoles derivatives were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that all of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. In particular, 3-(5-(4-(benzyloxy)-3-methoxyphenyl)-1-(4-(4-bromophenyl) thiazol-2-yl)-4,5-dihydro-1H-pyrazol-3-y l)-2H-chromen-2-one (7j) exhibited the most potent tyrosinase inhibitory activity with IC50 value 0.00458 +/- 0.00022 mu M compared with the IC50 value of kojic acid is 16.84 +/- 0.052 mu M. The inhibition mechanism analyzed by Lineweaver-Burk plots revealed that the type of inhibition of compound 7j on tyrosinase was noncompetitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compound 7a showed the highest binding affinity (-10.20 kcal/mol) with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compound 7j may serve as a structural template for the design and development of novel tyrosinase inhibitors. (C) 2017 Elsevier Inc. All rights reserved.