Design, synthesis, in vitro evaluation and molecular docking study of N′-Arylidene imidazo [1,2-a] pyridine-2-carbohydrazide derivatives as novel Tyrosinase inhibitors

A novel series of imidazo[1,2-r]pyridine 2-carbohudrazide derivatives bearing different arylidene pendantrs were designed, synthesized and evaluated for their inhibitory activity against mushroom Tyrosinase. It was found that compounds bearing 3-nitro (6j) and 4-hydroxy (6g) moieties on the arylidene pendant exhibited the best Tyrosinase inhibitory activity with IC50 values of 7.19 and 8.11 mu M, respectively. These results were comparable to that of kojic acid as the reference drug (IC50 = 9.64+0.5 mu M). Additionally, molecular docking analysis was performed to study the interactions and binding modes of compounds 6j, 6h and 6g which are showing the potential of two critical pi-pi interactions with His263 and Phe264 in the active site of Tyrosinase. The results indicated that 6j and 6g could be introduced as potent Tyrosinase inhibitors that might serve as promising candidates in medicine, cosmetics or food industry. (C) 2020 Elsevier B.V. All rights reserved.