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

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

doi:10.1016/j.heliyon.2023.e22009

Cited by 3 publications

(1 citation statement)

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“…Furthermore, the size of the substituent groups and the possibility of the Kojic moiety engaging with both copper ions are also determining factors for occupation of the enzyme binding pocket. 37 The comparison of their results with our data at the same concentration (50 μM) revealed that our synthetic pyridine derivatives showed overal higher inhibitory effects [∼50, 45, 75, 70, and 80% inhibition by compounds 1, 2, 3, 4 and 5, respectively, Figure S4 (Supporting Information)] and the calculated IC 50 values for our most potent inhibiting compounds (3, 4, and 5, with the IC 50 values of 12.0, 17.0, and 9.0 μM, respectively) were less than those from their reported potent inhibitors (compounds 4b, 4d, 4f, and 4h with the IC 50 values of 28, 22, 23, and 20 μM, respectively).…”

Section: Biochemistrymentioning

confidence: 99%

Inhibitory Effects, Fluorescence Studies, and Molecular Docking Analysis of Some Novel Pyridine-Based Compounds on Mushroom Tyrosinase

Lotfi Shahpar,

Mahdavi,

Mohamadnia

2024

Biochemistry

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Melanin biosynthesis in different organisms is performed by a tyrosinase action. Excessive enzyme activity and pigment accumulation result in different diseases and disorders including skin cancers, blemishes, and darkening. In fruits and vegetables, it causes unwanted browning of these products and reduces their appearance quality and economic value. Inhibiting enzyme activity and finding novel powerful and safe inhibitors are highly important in agriculture, food, medical, and pharmaceutical industries. In this regard, in the present study, some novel synthetic pyridine-based compounds including 2,6-bis (tosyloxymethyl) pyridine (compound 3), 2,6-bis (butylthiomethyl) pyridine (compound 4), and 2,6-bis (phenylthiomethyl) pyridine (compound 5) were synthesized for the first time, and their inhibitory potencies were assessed on mushroom tyrosinase diphenolase activity. The results showed that while all tested compounds significantly decreased the enzyme activity, compounds 4 and 5 had the highest inhibitory effects (respectively, 80 and 89% inhibition with the IC 50 values of 17.0 and 9.0 μmol L −1 ), and the inhibition mechanism was mixed-type for both compounds. Ligand-binding studies were carried out by fluorescence quenching and molecular docking methods to investigate the enzyme−compound interactions. Fluorescence quenching results revealed that the compounds can form nonfluorescent complexes with the enzyme and result in quenching of its intrinsic emission by the static process. Molecular docking analyses predicted the binding positions and the amino acid residues involved in the interactions. These compounds appear to be suitable candidates for more studies on tyrosinase inhibition.

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Section: Biochemistrymentioning

confidence: 99%