Synthesis of naproxen thiadiazole urea hybrids and determination of their anti-melanoma, anti-migration, tyrosinase inhibitory activity, and molecular docking studies

Abstract

Novel sixteen naproxen urea compounds were synthesized bearing the thiadiazole ring. Their inhibitory activities against tyrosinase were investigated. 3o was discovered to be the most potent inhibitor of tyrosinase, with an IC50 value of 35.0 µM. The kinetic parameters were used to determine the type of enzyme inhibition. The results showed that 3o was an uncompetitive inhibitor with the Ki value of 62.2 µM. Additionally, the cytotoxic effects of the synthesized compounds on melanoma (B16F10), mouse embryonic (3T3) and the healthy 3T3 cell lines were also investigated. According to the cytotoxicity results, 3e (IC50= 2.17 µM) showed the highest cytotoxicity on the B16F10 cells. Furthermore, the effects of selected compounds on the migration rate of melanoma cells were investigated. In addition, molecular modeling studies were also performed and the results showed the possible interactions between the uncompetitive inhibitor 3o with the Tyrosinase-L-Tyrosine enzyme substrate complex. © 2023 Elsevier B.V.