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Synthesis, in Vitro Evaluation and Molecular Docking of Amino-Kojic Acid Derivatives As Potent Tyrosinase and Urease Inhibitors Publisher



Ashooriha M ; Alizadeh S ; Khoshneviszadeh M ; Ansari M ; Kabiri M ; Mahdavi M ; Talebi M ; Mohammadi Khanaposhtani M ; Tahmasebi E ; Amanlou M ; Emami S
Authors

Source: Journal of Molecular Structure Published:2026


Abstract

In this study we have synthesized several amino-kojic acid derivatives by replacing the alcoholic hydroxyl group of kojic acid with cyclic amines including piperazine and piperidine derivatives (4a-g and 6a-d). The in vitro anti-mushroom tyrosinase assay revealed that all compounds with the exception of 4-methylpiperidine derivative 6b had more potent activity than the parent compound kojic acid. Certainly, the 4-methoxyphenyl-piperazine derivative 4c with IC50 value of 0.12 µM was 156 times more potent than kojic acid. Furthermore, all compounds were tested against another metalloenzyme namely jack bean urease. Interestingly, the 4-methylpiperidine derivative 6b with the lowest inhibitory activity against tyrosinase was the most active compound against urease (IC50 = 6.31 µM). However, the 4-methoxyphenyl-piperazine analog (4c) also showed high activity (IC50 = 6.74 µM) against urease, being more potent than thiourea. The DPPH radical scavenging assay indicated that the representative compound 4c has respectable antioxidant activity. According to the docking results, compound 4c attached to the tyrosinase’s active site with a binding energy (BE) value lower than that of kojic acid. Also, the latter compound with BE value of -6.36 Kcal/mole formed three H-bonds with the urease’s active site and coordinated with the nickel center. The results of this study is highlighted the amino-kojic acid derivatives as potent leads for the development of anti-tyrosinase and anti-urease agents useful in the food and agricultural industries. © 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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