Synthesis and Biological Evaluation of Di-Substituted Thiotriazole Linked to Quinazolinone as a Tyrosinase Inhibitor

Subject Areas : Applied Chemistry

Alireza Sherafati ¹ , Shahram Moradi ^{2 *} , Mohammad Mahdavi ³ , Ali Mahmoodi ⁴

1 - Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
2 - Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran
3 - Endocrinology and Metabolism Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
4 - Department of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran

Received: 2024-11-10 Accepted : 2025-02-04 Published : 2025-07-07

Keywords: Molecular docking, Tyrosinase, Thiotriazole, Quinazolinone,

Abstract :

In this study, a series of di-substituted thiotriazole linked to quinazolinone derivatives (6a–p) were synthesized and evaluated for their tyrosinase inhibitory activity. The inhibitory activities of the compounds were measured and compared to the reference inhibitor, kojic acid. Compound 6n (R1: benzyl, R2: 4-nitrophenyl) exhibited the most potent inhibition (IC50 = 16.26 ± 2.57 µM), surpassing kojic acid (IC50 = 23.6 ± 2.56 µM). Molecular docking studies provided further insight into the binding interactions of compound 6n, demonstrating key hydrogen bonding and π-π stacking interactions with important residues such as Val283, Phe264, His244, and Asn81. These findings suggest that the substituted thiotriazole linked to quinazolinone derivatives hold promise as potent tyrosinase inhibitors, with potential therapeutic applications in the treatment of hyperpigmentation disorders and other melanin-related conditions.