Design, synthesis, in vitro, and in silico evaluations of kojic acid derivatives linked to amino pyridine moiety as potent tyrosinase inhibitors
Davood Rezapour Niri,
Mohammad Hosein Sayahi,
Somayeh Behrouz,
Ali Moazzam,
Fatemeh Rasekh,
Nader Tanideh,
Cambyz Irajie,
Mohammad Seif Nezhad,
Bagher Larijani,
Aida Iraji,
Mohammad Mahdavi
Affiliations
Davood Rezapour Niri
Medicinal Chemistry Research Laboratory, Department of Chemistry, Shiraz University of Technology, Shiraz, Iran
Mohammad Hosein Sayahi
Department of Chemistry, Payame Noor University (PNU), Tehran, Iran
Somayeh Behrouz
Medicinal Chemistry Research Laboratory, Department of Chemistry, Shiraz University of Technology, Shiraz, Iran
Ali Moazzam
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran, Iran
Fatemeh Rasekh
Medicinal Chemistry Research Laboratory, Department of Chemistry, Shiraz University of Technology, Shiraz, Iran; Department of Chemistry, Payame Noor University (PNU), Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran, Iran; Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Biology, Payame Noor University (PNU), Tehran, Iran
Nader Tanideh
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Cambyz Irajie
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Seif Nezhad
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Bagher Larijani
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran, Iran
Aida Iraji
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Corresponding author. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Mohammad Mahdavi
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran, Iran; Corresponding author. Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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.
