Cu(II)-Promoted the Chemical Synthesis of New Azines-Based Naphthalene Scaffold as In Vitro Potent Mushroom Tyrosinase Inhibitors and Evaluation of Their Antiproliferative Activity

Abstract

Herein, synthesis of new designated azines-based naphthalene scaffold (3a–10) was assisted by CuCl2.2H2O for the first time. Their biological screening manifested that azines 3a, 4, 7, 9, and 10 exhibit effectual mushroom tyrosinase inhibition with IC50 values within the ambit of 3.75–12.36 µM. Mostly, azines 4 and 9 demonstrated about four-fold enhancement in the activity (IC50 = 3.91 ± 0.16, 3.75 ± 0.15 µM, respectively) comparable to the kojic acid (IC50 = 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 IC50 values of 4.35 ± 0.18 and 2.41 ± 0.12 µM, respectively. Whereas 9 was the most robust azine toward HepG2 with an IC50 value of 2.19 ± 0.12 µM. Exhaustively, azines 4 and 9 could be promising biomedical lead candidates.