Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches.
Chem Biodivers
; 20(5): e202201220, 2023 May.
Article
in En
| MEDLINE
| ID: mdl-37043708
ABSTRACT
A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined inâ
vitro. GR and GST were isolated from human erythrocytes with 7.63â
EU/mg protein and 5.66â
EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4-amino-3-bromo-5-fluorobenzoate with Ki value of 0.325±0.012â
µM) and compound 5 (methyl 4-amino-2-nitrobenzoate with Ki value of 92.41±22.26â
µM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer-aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4-amino-2-bromobenzoate) and 6 (methyl 4-amino-2-chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glutathione
/
Antioxidants
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Chem Biodivers
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2023
Document type:
Article