Computer-assisted discovery of tyrosinase inhibitors from turmeric and clove: An in silico study on natural skin whitening agents and their potential toxicity

A computational approach was employed to identify potential tyrosinase-related protein 1 (TYRP1) inhibitors from turmeric and clove extracts, with the goal of discovering safer alternatives to the toxic hydroquinone for skin whitening applications. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed the phytochemical composition of the plant extracts, which were then evaluated for their binding affinity to TYRP1 through molecular docking simulations. The stability of the resulting hit compounds was assessed via molecular dynamics simulations, and their dermal toxicity profiles were determined using Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis. Density Functional Theory (DFT) calculations were also performed to compare the chemical reactivity of the hit compounds to hydroquinone. The results identified 3,4-dimethoxybenzamidoxime from clove and Ar-turmerone from turmeric as potential inhibitors, exhibiting binding free energies of-6.8 kcal/mol and-6.6 kcal/mol, respectively. These values surpass those of hydroquinone (-5.1 kcal/mol) and the native ligand (-5.5 kcal/mol), suggesting potential inhibitory activity. Notably, 3,4-dimethoxybenzamidoxime exhibited favorable skin permeation properties and passed all toxicity tests, suggesting its potential as a safe and effective replacement for hydroquinone in skin whitening products. (c) 2024 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.