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

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

Yousefnejad F¹ ; Iraji A^{2, 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

Show Affiliations

1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3. Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
4. Drug and Food Control Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
5. Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
6. Department of Medical Mycology and Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
7. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
8. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

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.

Style	Citing Format
MLA	Yousefnejad F, et al.. "Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis." Chemistry and Biodiversity, vol. 20, no. 1, 2023, pp. -.
APA	Yousefnejad F, Iraji A, Sabourian R, Moazzam A, Tasharoie S, Sara Mirfazli S, Zomorodian K, Alireza Akhlagh S, Hosseini S, Larijani B, Tehrani MB, Hajimahmoodi M, Mahdavi M (2023). Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis. Chemistry and Biodiversity, 20(1), -.
Chicago	Yousefnejad F, Iraji A, Sabourian R, Moazzam A, Tasharoie S, Sara Mirfazli S, Zomorodian K, et al.. "Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis." Chemistry and Biodiversity 20, no. 1 (2023): -.
Harvard	Yousefnejad F et al. (2023) 'Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis', Chemistry and Biodiversity, 20(1), pp. -.
Vancouver	Yousefnejad F, Iraji A, Sabourian R, Moazzam A, Tasharoie S, Sara Mirfazli S, et al.. Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis. Chemistry and Biodiversity. 2023;20(1):-.
BibTex	@article{ author = {Yousefnejad F and Iraji A and Sabourian R and Moazzam A and Tasharoie S and Sara Mirfazli S and Zomorodian K and Alireza Akhlagh S and Hosseini S and Larijani B and Tehrani MB and Hajimahmoodi M and Mahdavi M}, title = {Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis}, journal = {Chemistry and Biodiversity}, volume = {20}, number = {1}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Yousefnejad F AU - Iraji A AU - Sabourian R AU - Moazzam A AU - Tasharoie S AU - Sara Mirfazli S AU - Zomorodian K AU - Alireza Akhlagh S AU - Hosseini S AU - Larijani B AU - Tehrani MB AU - Hajimahmoodi M AU - Mahdavi M TI - Ugi Bis-Amide Derivatives As Tyrosinase Inhibitor; Synthesis, Biology Assessment, and in Silico Analysis JO - Chemistry and Biodiversity VL - 20 IS - 1 SP - EP - PY - 2023 ER -

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Abstract