Methyl benzoate derivatives as inhibitors of pentose phosphate pathway, which promotes cancer progression and drug resistance: An in silico study supported by in vitro results

Kesebir, Arzu Öztürk; Güller, Pınar; Kalın, Ramazan; Özdemir, Haşan; Küfrevioğlu, Ömer İrfan

doi:10.1002/bab.2322

Cited by 5 publications

(3 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the light of this information, the inhibition effects of methyl 4‐aminobenzoate derivatives on GST and GR activities, which are active in the GSH system, were investigated in our study. It was reported that methyl benzoate derivatives had high inhibitory effects on some metabolic enzymes such as human erythrocyte glucose 6‐phosphate dehydrogenase (G6PD), 6‐phosphogluconate dehydrogenase (6PGD), human serum paraoxonase 1 (PON1) α‐amylase, and α‐glucosidase in a micro molar range [39–41] …”

Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Korkmaz¹,

Güller²,

Kalın³

et al. 2023

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Korkmaz¹,

Güller²,

Kalın³

et al. 2023

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

show abstract

“…They determined that the cinnamic derivatives showed the most active properties. Kesebir [31] investigated methyl 4-aminobenzoates on 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase activity. Methyl 4-amino-2-nitrobenzoate displayed the best inhibitor property against glucose 6-phosphate dehydrogenase (K i : 117.8 � 15.7 μM) and methyl 4-amino-2-chlorobenzoate displayed the best inhibitor property against 6-phosphogluconate dehydrogenase enzyme activity (K i : 82.3 � 3.9 μM).…”

Section: Resultsmentioning

confidence: 99%

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Abul

Gerni

Korkmaz

et al. 2023

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

Lactoperoxidase enzyme (LPO) is secreted from salivary, mammary, and other mucosal glands including the bronchi, lungs, and nose, which had functions as a natural and the first line of defense towards viruses and bacteria. In this study, methyl benzoates were examined in LPO enzyme activity. Methyl benzoates are used as precursors in the synthesis of aminobenzohydrazides used as LPO inhibitors. For this purpose, LPO was purified in a single step using sepharose‐4B‐l‐tyrosine‐sulfanilamide affinity gel chromatography with a yield of 9.91 % from cow milk. Also, some inhibition parameters including the half maximal inhibitory concentration (IC50) value and an inhibition constant (Ki) values of methyl benzoates were determined. These compounds inhibited LPO with Ki values ranging from 0.033±0.004 to 1540.011±460.020 μM. Compound 1 a (methyl 2‐amino‐3‐bromobenzoate) showed the best inhibition (Ki=0.033±0.004 μM). The most potent inhibitor (1 a) showed with a docking score of −3.36 kcal/mol and an MM‐GBSA value of −25.05 kcal/mol, of these methyl benzoate derivatives (1 a–16 a) series are established H‐bond within the binding cavity with residues Asp108 (distance of 1.79 Å), Ala114 (distance of 2.64 Å), and His351 (distance of 2.12 Å).

show abstract

“…IC 50 was defined as the concentration of the compound causing 50 % inhibition, and it was calculated based on Activity (%)–[usnic and carnosic acid] plots for each compound [23,24] . The K i values and inhibition types were found using Lineweaver‐Burk plots [25,26] …”

Section: Methodsmentioning

confidence: 99%

Effects of Carnosic and Usnic Acid on Pentose Phosphate Pathway Enzymes: An Experimental and Molecular Docking Study

Demir,

Öztürk,

Isıyel

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Abstract6‐phosphogluconate dehydrogenase (6PGD) and Glucose‐6‐phosphate dehydrogenase (G6PD) are crucial enzymes involved in generating cellular reducing power. Modifying the balance of reduced NADPH is considered essential for cancer advancement and combined therapeutic strategies. Usnic acid (UA) is a physiologically active dibenzofuran derivative. Carnosic acid (CA) is a phenolic diterpene that has been isolated from several plants. This work evaluated the inhibitory effects of UA and CA on G6PD and 6PGD by in vitro tests. Molecular docking studies were employed to predict the mechanisms of inhibition. IC50 values for UA and CA were determined to be 49.50 μM and 77.00 μM for G6PD, and 69.30 μM and 57.75 μM for 6PGD, respectively. The Ki values for UA and CA were determined to be 35.01±7.69 μM and 43.46±10.48 μM for G6PD, and 104.87±11.86 μM and 31.17±2.55 μM for 6PGD, respectively. UA was identified as the most effective inhibitor against G6PD, whereas CA exhibited the best inhibitory activity against 6PGD, with estimated binding energies of −8.0 and −7.8 kcal/mol, respectively, in molecular docking studies. Ultimately, it was shown that the results obtained from in vitro and in silico methods in the study were strongly associated. These chemicals′ structure might assist in creating medications that focus on the pentose phosphate pathway.

show abstract

Methyl benzoate derivatives as inhibitors of pentose phosphate pathway, which promotes cancer progression and drug resistance: An in silico study supported by in vitro results

Cited by 5 publications

References 59 publications

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Effects of Carnosic and Usnic Acid on Pentose Phosphate Pathway Enzymes: An Experimental and Molecular Docking Study

Contact Info

Product

Resources

About