Design, synthesis, in vitro, and in silico evaluations of kojic acid derivatives linked to amino pyridine moiety as potent tyrosinase inhibitors

• Published in: Heliyon Vol. 9; no. 11; p. e22009
• Main Authors: Rezapour Niri, Davood, Sayahi, Mohammad Hosein, Behrouz, Somayeh, Moazzam, Ali, Rasekh, Fatemeh, Tanideh, Nader, Irajie, Cambyz, Seif Nezhad, Mohammad, Larijani, Bagher, Iraji, Aida, Mahdavi, Mohammad
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2023; Elsevier
• Subjects: Antioxidant; Kojic acid; Molecular dynamic simulation; Synthesis; Tyrosinase inhibition; Tyrosinase inhibition; Synthesis; Molecular dynamic simulation; Antioxidant; Kojic acid
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e22009

In the present study, novel series of kojic acid derivatives conjugated to amino pyridine moiety were designed and synthesized to explore their inhibitory activity against tyrosinase. To this end, the structure of all derivatives was characterized by 1H NMR, 13C NMR, FT-IR, and elemental analysis. Next, all derivatives were evaluated against tyrosinase compared to the kojic acid as positive control and exhibited different inhibitory potencies. Furthermore, the antioxidant potential of all derivatives was determined. The kinetic analysis of the most active agent revealed that 3-hydroxy-6-(hydroxymethyl)-2-((3-nitrophenyl)(pyridin-2-ylamino)methyl)-4H-pyran-4-one (4h) binds to the enzyme in the uncompetitive mode of action. The docking analysis and molecular dynamic simulations showed considerable binding affinity and significant interactions with tyrosinase enzyme to target the melanogenesis pathway, proposing them as potent candidates to control hyperpigmentation in the future.