Investigations of Some Chlorocresol Hydrazones Against Tyrosinase Enzyme by Molecular Docking Method: In Silico Study

Abstract

Introduction: Tyrosinase, found in various organisms, including plants and mammals, and is responsible for pigmentation as well as the undesirable browning of fruits and vegetables, is a multi-copper enzyme involved in the synthesis of melanin in human. As it is known, melanin provides protection against harmful ultraviolet radiation, which can lead to serious conditions like skin cancers. However, excessive melanin accumulation could result in hyperpigmented spots, creating aesthetic concerns. Tyrosinase inhibitors could potentially lead to the development of novel skin-whitening agents, anti-browning compounds for food preservation, and also for insect control substances. Recently, a wide spectrum of numerous moderate to potent tyrosinase inhibitors have been identified and reported.

Methods: In this study, by using the AutodockVina Virtual Screening Tool,  some hydrazide-hydrazone compounds starting from p-chlorocresol were screened for interactions and binding mode of the tyrosinase active site. The enzyme-ligand interactions were analyzed using Biovia Discovery Studio software. Moreover, drug-likeness potential of the compounds was examined by using SwissADME online web tool.

Results: The results showed that compound S5, which did not violate the Lipinski and Veber rules and had a binding energy of -7.9 kcal/mol, could be a potential inhibitor of the tyrosinase enzyme.

Conclusion: Identifying the interactions between the tested ligands and the tyrosinase enzyme will contribute to the development of new hydrazide-hydrazone derivatives aiming the inhibition of tyrosinase.