Abstract
Herein, synthesis of new designated azines-based naphthalene scaffold (3a-10) was assisted by CuCl
2
.2H
2
O for the first time. Their biological screening manifested that azines 3a, 4, 7, 9, and 10 exhibit effectual mushroom tyrosinase inhibition with IC
50
values within the ambit of 3.75-12.36 µM. Mostly, azines 4 and 9 demonstrated about four-fold enhancement in the activity (IC
50
= 3.91 ± 0.16, 3.75 ± 0.15 µM, respectively) comparable to the kojic acid (IC
50
= 16.86 ± 0.84 µM). Molecular docking of azines 4 and 9 against mushroom tyrosinase (2Y9X) proved the significant rule of isatin moiety (4) in hydrogen bonding, the importance of 4-dimethylamino styryl unit (9) in hydrophobic interactions, and the overall findings confirmed the momentousness of azine group (N-N) and naphthalene scaffold in the interactions with the histidine key residues of the tyrosinase binding pocket. Evaluation of antiproliferative activity indicated that, azine 4 was the most potent one against both MCF-7 and HCT116 with IC
50
values of 4.35 ± 0.18 and 2.41 ± 0.12 µM, respectively. Whereas 9 was the most robust azine toward HepG2 with an IC
50
value of 2.19 ± 0.12 µM. Exhaustively, azines 4 and 9 could be promising biomedical lead candidates.