Effect of some phenolic compounds on glucose-6 phosphate dehydrogenase enzyme activity

Cancer is currently one of the most common health problems, both in terms of prevalence and its significant financial and workload impact on the healthcare system. One of the new therapeutic targets in cancer treatment is the enzyme glucose-6-phosphate dehydrogenase (G6PD), which is overproduced in some types of cancer, and its inhibition is emerging as a potential treatment strategy. Through the reactions catalyzed by G6PD, nicotinamide adenine dinucleotide phosphate (NADPH), which is used in cellular biosynthetic processes, is produced, and at the end of the pentose phosphate pathway, ribose-5-phosphate, a building block for molecules such as DNA and RNA, is synthesized. In this thesis, the inhibitory effects of some flavonoid compounds on G6PD were tested in vitro. The results showed that baicalein was the most effective inhibitor, with an IC50 value of 13.72 µM, while the IC50 values for apigenin, morin, and fisetin were calculated as 17.70, 18.94, and 22.49 µM, respectively. The interactions of these molecules with the enzyme's active site were examined using molecular docking studies, and the stability of the complexes formed with G6PD in a semi-realistic environment was assessed using molecular dynamics simulations. Both in vitro and in silico data corroborated each other, leading to the conclusion that Baicalein is the most effective inhibitor for G6PD. Furthermore, the potential for these flavonoids to be used as active pharmaceutical ingredients was demonstrated through ADME analysis.