Research Article
Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches
Işıl Nihan Korkmaz,
Uğur Güller,
Ramazan Kalın,
Hasan Özdemir,
Ömer İrfan Küfrevioğlu,
Işıl Nihan Korkmaz
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorCorresponding Author
Uğur Güller
Department of Food Engineering, Faculty of Engineering, Iğdır University, Iğdır, 76100, Türkiye
Search for more papers by this authorRamazan Kalın
Department of Basic Science, Faculty of Science, Erzurum Technical University, Erzurum, 25700 Türkiye
Search for more papers by this authorHasan Özdemir
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorÖmer İrfan Küfrevioğlu
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorIşıl Nihan Korkmaz,
Uğur Güller,
Ramazan Kalın,
Hasan Özdemir,
Ömer İrfan Küfrevioğlu,
Işıl Nihan Korkmaz
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorCorresponding Author
Uğur Güller
Department of Food Engineering, Faculty of Engineering, Iğdır University, Iğdır, 76100, Türkiye
Search for more papers by this authorRamazan Kalın
Department of Basic Science, Faculty of Science, Erzurum Technical University, Erzurum, 25700 Türkiye
Search for more papers by this authorHasan Özdemir
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorÖmer İrfan Küfrevioğlu
Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, 25240 Türkiye
Search for more papers by this authorAbstract
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 in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 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±0.012 μM) and compound 5 (methyl 4-amino-2-nitrobenzoate with Ki value of 92.41±22.26 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.
Graphical Abstract
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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