The synthesis of N-benzoylindoles as inhibitors of rat erythrocyte glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) play an important function in various biochemical processes as they generate reducing power of the cell. Thus, metabolic reprogramming of reduced nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis is reported to be a vital step in cancer progression as well as in combinational therapeutic approaches. In this study, N-benzoylindoles 9a--9d, which form the main framework of many natural indole derivatives such as indomethacin and N-benzoylindoylbarbituric acid, were synthesized through three easy and effective steps as an in vitro inhibitor effect of G6PD and 6PGD. The N-benzoylindoles inhibited the enzymatic activity with IC50 in the range of 3.391505 μM for G6PD and 2.19–990 μM for 6PGD. © 2018 Wiley Periodicals, Inc.