Ligand Engineering Based on Kojic Acid for Safe Tyrosinase Inhibition in Cosmetic and Agricultural Industries

Subject Areas : Shelf Life of Food Products and Agricultural Productions

Reza Farrokhi ^{1 *} , Dadkhoda Ghazanfari ²

1 - Department of Chemistry, KeC., Islamic Azad University, Kerman, Iran
2 - Department of Chemistry, KeC., Islamic Azad University, Kerman, Iran

Received: 2025-07-04 Accepted : 2025-07-27 Published : 2025-08-03

Keywords: Tyrosinase, Molecular docking, Low-toxicity inhibitor, Melanogenesis, Agriculture, Kojic acid,

Abstract :

Tyrosinase is a key enzyme in the melanogenesis pathway, and its inhibition plays a crucial role in treating pigmentation disorders and preventing enzymatic browning in agricultural products. Conventional tyrosinase inhibitors such as kojic acid and hydroquinone, although effective, pose significant clinical limitations due to toxicity and carcinogenic risks. In this study, a novel ligand with the molecular formula C₁₄H₂₂O₄ was designed using molecular docking and in silico drug design techniques to inhibit tyrosinase more safely and effectively. Active sites of the enzyme were identified using Molegro Virtual Docker, and docking simulations were performed via PyRx. Comparative analysis revealed that the engineered ligand exhibited stronger binding affinity than kojic acid, with a significantly higher LD₅₀ (over sevenfold) and no evidence of toxicity or carcinogenicity. ADME-Tox and ProTox analyses confirmed the compound’s pharmacological safety. The findings suggest that this engineered ligand is a promising low-toxicity tyrosinase inhibitor with potential applications in cosmetics, pharmaceuticals, and agriculture particularly for enhancing postharvest stability of crops by reducing enzymatic browning.

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