The synthesis of new oxindoles as analogs of natural product 3,3′-bis(indolyl)oxindole and in vitro evaluation of the enzyme activity of G6PD and 6PGD

Abstract

Natural and synthetic derivatives that contain an indole core are being used in medical treatments and technological processes. Therefore, the development of new synthetic methods for the synthesis of indole derivatives is very popular. In this study, new oxindoles with reaction of 4,7-dihydro-1 H -indole (2) and isatin (4) were synthesized as analogs of natural product 3,3 ′ -bis(indolyl)oxindole. The biological properties of the compounds obtained during this study were also studied, showing that compounds 5, 7, and 12 inhibited the activity of G6PD with an IC 50 of 99 µ M, 231 µ M, and 304 µ M respectively. The activity of rat erythrocyte 6PGD was increased in the presence of 5 and 7 and was inhibited in the presence of 12. As indole derivative 5 was an activator of 6PGD and inhibitor of G6PD, it was selected for docking studies to understand the mechanism of activation and inhibition.

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

“…[13,[21][22][23][24] To date, only a few G6PD inhibitors have been available with high IC 50 values, which negatively affect their use as therapeutics and basic research probes. [13,[21][22][23][24] To date, only a few G6PD inhibitors have been available with high IC 50 values, which negatively affect their use as therapeutics and basic research probes.…”

“…[13,38,39] It is of interest that these groups have free electrons and suitable geometries that can easily interact with the active site amino acids in the structure of the enzymes. In our work, the results demonstrated that the derivatives containing N-substituted indolines had no effect on the activity of G6PD and 6PGD whereas the compounds with N-benzoylindoles inhibited the enzymatic activ- In the current research, it has been determined that organic molecules containing sulfur, nitrogen, oxygen, and halide groups in the structure of molecules are strong inhibitors of enzymes.…”

“…[13] Another remarkable subject is the question of why N-substituted indolines do not affect the enzymatic activity. [13] Another remarkable subject is the question of why N-substituted indolines do not affect the enzymatic activity.…”

“…Therefore, a great deal of attention has been given to develop effective, facile, and innovative synthetic strategies for the development of the indole chemistry. [9][10][11][12][13][14][15] While a number of methods have already been published for the synthesis of 3-substituted indole derivatives, there are only few methods for the synthesis of 2-or N-substituted indole derivatives through the indole (1) ring (Figure 1). An alternative method that utilizes indoline (4) for an easy and effective synthesis of N-substituted indoles was developed by Saracoglu and group.…”

The effect of astaxanthin and cadmium on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzymes activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro

“…[51] Çiftci et al [52] investigated effect of some plant hormones on rat erythrocyte G6PD enzyme activity. Bayındır et al [53] investigated in vitro effect of new oxindoles derivatives on rat erythrocyte G6PD and 6PGD enzymes activity. Another study deals with effect of ethanol on rat and human erythrocyte G6PD enzyme activity.…”