Article 2025 · 3 citations

<i>In vitro</i> inhibition potency of malononitrile derivatives on the activity of two pentose phosphate pathway enzymes: accompanied by molecular docking evaluation

Kesebir, Arzu Ozturk, Dagalan, Ziya, Guller, Pinar, Nisanci, Bilal, Kufrevioglu, Omer Irfan

Abstract

Many disorders, including cancer and malaria, could be targeted via the pentose phosphate pathway (PPP), whose products are key in biosynthetic reactions in cells. The goal of this study was to find new PPP inhibitors. The inhibition effects of malononitrile derivatives on Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through in vitro experiments. Besides, molecular docking studies were performed to predict the interactions having role in inhibition of compounds. Ki constants of derivatives were found between 4.24 +/- 0.46-69.63 +/- 7.75 mu M for G6PD and 1.91 +/- 0.12-95.07 +/- 11.08 mu M for 6PGD. Derivatives indicated non-competitive inhibition on both enzymes except for compound 4. The findings of the molecular docking studies revealed that free-binding energy estimations agreed with in vitro data. The structure of these malononitrile derivatives may guide for drug discovery in targeting the PPP.

Keywords

malononitrile derivatives pentose phosphate pathway inhibition structure-activity relationship 6-PHOSPHOGLUCONATE DEHYDROGENASE OXIDATIVE STRESS GLUCOSE-6-PHOSPHATE-DEHYDROGENASE GLYCOLYSIS TKTL1

WoS Categories

Biochemistry & Molecular Biology Pharmacology & Pharmacy

Sustainable Development Goals

Good Health and Well-being

Citation

Journal: ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES
Year: 2025
Volume: 80
Issue: 1-2
Pages: 33-40
ISSN: 0939-5075
eISSN: 1865-7125
DOI: 10.1515/znc-2023-0164
WoS UID: WOS:001186600300001

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