Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl)pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies.

BACKGROUND Aiming of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. OBJECTIVE The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. METHODOLOGY MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the tyrosinase (TYR) inhibitory activity of the targets. RESULTS The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitor test. Compounds 2a, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the structure-activity relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. CONCLUSION The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.