Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

Abstract

Glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconate dehydrogenase (6PGD) are pentose phosphate pathway enzymes. Compounds with a heterocyclic pyrrole ring system containing this atom can be derivatized with various functional groups into highly effective bioactive agents. In this study, pyrrole derivatives on these enzyme's activity were investigated. The IC50 values of different concentrations of pyrrole derivatives for G6PD were found in the range of 0.022–0.221 mM Ki values 0.021 ± 0.003–0.177 ± 0.021 and for 6PGD IC50 values 0.020–0.147, mM Ki values 0.013 ± 0.002–0.113 ± 0.030 mM. The 2‐acetyl‐1‐methylpyrrole (1g) showed the best inhibition value for G6PD and 6PGD enzymes. In addition, in silico molecular docking experiments were performed to elucidate how these pyrrole derivatives (1a–g) interact with the binding sites of the target enzymes. The study's findings on pyrrole derivatives could be used to create innovative therapeutics that could be a treatment for many diseases, especially cancer manifestations.