Methyl benzoate derivatives as inhibitors of pentose phosphate pathway, which promotes cancer progression and drug resistance: An in silico study supported by in vitro results

The pentose phosphate pathway (PPP), whose products are vital in biosynthetic events, is targeted in the treatment of many diseases such as cancer and malaria. The objective of this study was to identify new PPP inhibitors. The inhibition effects of methyl 4-amino benzoates on glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through in vitro experiments and molecular docking studies were used to estimate inhibition mechanisms. IC50 values of compounds were found between 100.8 and 430.8 mu M for G6PD and 206 and 693.2 mu M for 6PGD. Molecular docking analysis showed that compound 1 was found the most effective inhibitor against hG6PD and compound 4 had the highest inhibitory potency against h6PGD with the estimated binding energy of -6.71 and -7.61 kcal/mol, respectively. In conclusion, it was determined that in vitro and in silico outcomes of the study were highly correlated with each other. The structure of these benzoates may aid in the development of drugs that target the PPP.

Automated summary

This study identified new inhibitors of the pentose phosphate pathway (PPP) and determined their inhibitory mechanisms through a combination of experimental and computational methods. The results showed that certain compounds exhibited significant inhibition of G6PD and 6PGD, providing a new structural basis for the development of drugs targeting the PPP.