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Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis Publisher Pubmed



Yousefnejad F1 ; Iraji A2, 3 ; Sabourian R4 ; Moazzam A1 ; Tasharoie S4 ; Sara Mirfazli S5 ; Zomorodian K6 ; Alireza Akhlagh S7 ; Hosseini S1 ; Larijani B1 ; Tehrani MB8 ; Hajimahmoodi M4 ; Mahdavi M1
Authors

Source: Chemistry and Biodiversity Published:2023


Abstract

Herein, a straightforward synthetic strategy mediated by Ugi reaction was developed to synthesize novel series of compounds as tyrosinase inhibitors. The structures of all compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, and CHNOS techniques. The tyrosinase inhibitory activities of all synthesized derivatives 5a–m were determined against mushroom tyrosinase and it was found that derivative 5c possesses the best inhibition with an IC50 value of 69.53±0.042 μM compared to the rest of the synthesized derivatives. Structure–activity relationships (SARs) showed that the presence of 4-MeO or 4-NO2 at the R2 position plays a key role in tyrosinase inhibitory activities. The enzyme kinetics studies showed that compound 5c is an noncompetitive inhibitor. For in silico study, the allosteric site detection was first applied to find the appropriate binding site and then molecular docking and molecular dynamic studies were performed to reveal the position and interactions of 5c as the most potent inhibitor within the tyrosinase active site. The results showed that 5c bind well with the proposed binding site and formed a stable complex with the target protein. © 2022 Wiley-VHCA AG, Zurich, Switzerland.
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