Synthesis and molecular modeling of new 2‐benzylidenethiobarbituric acid derivatives as potent tyrosinase inhibitors agents. Issue 4 (3rd April 2022)

• Record Type: Journal Article
• Authors: Najafi, Zahra; Kamari‐aliabadi, Adel; Sabourian, Reyhaneh; Hajimahmoodi, Mannan; Chehardoli, Gholamabbas
• Is Part Of: Journal of the Chinese Chemical Society. Volume 69:Issue 4(2022)
• Page Start: 692
• Page End: 702
• Publication Date: 2022-04-03
• Subjects: docking study -- melanogenesis -- synthesis -- thiobarbituric acid -- tyrosinase inhibitors; Chemistry -- Periodicals; Electronic journals; 540.5
• DOI: 10.1002/jccs.202100537
• Languages: English
• ISSNs: 0009-4536

Abstract

Abstract: New 2‐benzylidenethiobarbituric acid‐(benzyloxyphenyl) derivatives were designed, synthesized, and evaluated as tyrosinase inhibitors. The products can be divided into two groups: 4‐hydroxybenzaldehyde derivatives and vanillin derivatives. Some of the 4‐hydroxybenzaldehyde derivatives showed significant inhibitory activity while all vanillin derivatives have no inhibitory activities. It seems that the presence of the methoxy group on the internal aromatic ring prevents the ligand–enzyme interaction. According to the tyrosinase inhibitory assay, 5‐(4‐([4‐Methylbenzyl]oxy)benzylidene)‐2‐thioxodihydropyrimidine‐4, 6(1H, 5H)‐dione (4g ) is the most potent antityrosinase agents with an IC50 value of 23.90 ± 0.08 μM. It showed even better inhibitory activity than kojic acid. The results of kinetic and molecular docking studies demonstrated that compound 4g acts as a noncompetitive inhibitor and can bind to some amino acids such as His263 and Val283 of the active site through Pi–alkyl and Pi–Pi interactions and areas around the active site via the hydrogen bond. In‐silico adsorption, distribution, metabolism, excretion, and toxicity (ADMET) studies predicted that these products have good drug‐likeness. All findings indicate the 2‐benzylidenethiobarbituric acids with the benzyloxyphenyl tail have good potential for the treatment of melanogenesis compared to kojic acid. Abstract : Chehardoli et al. designed, synthesizedsome new 2‐benzylidenethiobarbituric acid‐(benzyloxyphenyl) derivatives and evaluated them as tyrosinase inhibitors. Among these products, 5‐(4‐((4‐Methylbenzyl)oxy)benzylidene)‐2‐thioxodihydropyrimidine‐4, 6(1H, 5H)‐dione (4g) is the most potent anti‐tyrosinase agents with an IC50 value of 23.90 ± 0.08 μMthat has better inhibitory activity than kojic acidas a positive control.