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

Abstract

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. K i constants of derivatives were found between 4.24 ± 0.46–69.63 ± 7.75 µM for G6PD and 1.91 ± 0.12–95.07 ± 11.08 µM 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.