Evaluating the effects of disubstituted 3-hydroxy-1H-pyrrol-2(5H)-one analog as novel tyrosinase inhibitors

• Published in: Bioorganic chemistry 2022-09, Vol.126, p.105876-105876, Article 105876
• Main Authors: Alizadeh, Naiemeh, Hossein Sayahi, Mohammad, Iraji, Aida, Yazzaf, Rozita, Moazzam, Ali, Mobaraki, Koroush, Adib, Mehdi, Attarroshan, Mahshid, Larijani, Bagher, Rastegar, Hossein, Khoshneviszadeh, Mehdi, Mahdavi, Mohammad
• Format: Article
• Language: English
• Subjects: 3-hydroxy-1H-pyrrol-2(5H)-one; Molecular docking; Synthesis; Tyrosinase inhibitors
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.105876

[Display omitted] •A series of disubstituted 3-hydroxy-1H-pyrrol-2(5H)-one derivatives were designed and synthesized as anti-tyrosinase agents.•6a showed exceptionally high potency against tyrosinase with an IC50 value of 6.98 ± 1.05 µM.•Kinetic study of 6a confirmed mixed inhibitory activity against tyrosinase.•Antioxidant potencies, as well as molecular docking studies of this set of compounds, were also performed. In the present study, a series of 3-hydroxy-1H-pyrrol-2(5H)-one derivative were rationally designed and synthesized. The structure of targeted compounds was confirmed by IR, 1H NMR, 13C NMR, and elemental analysis. Next, all derivatives were evaluated as tyrosinase inhibitors, and among the synthesized derivatives, compound 6a was proved to be the most potent inhibitor with an IC50 value of 6.98 ± 1.05 µM. Kinetic study of compound 6a confirmed the mixed type of inhibitory activity towards tyrosinase. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase and exhibited interaction with important residues of the binding site.