Identification of Glucose-6-Phosphate Dehydrogenase (G6PD) Inhibitors by Cheminformatics Approach.

Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme in the pentose phosphate pathway (PPP), a critical glucose metabolism pathway linked to cancer cell proliferation and metastasis. Inhibiting the PPP presents a promising approach to cancer treatment. The G6PD enzyme structure was obtained from the Protein Data Bank (PDB). The active site responsible for NADP+ binding was identified and used for structure-based pharmacophore design. This pharmacophore model was applied to the ZINC database to screen for small molecules. Molecular docking was accomplished using AutoDock Vina, and protein-ligand interactions were analyzed. Additionally, compounds were validated based on in silico ADMET properties to select the most promising candidates. A comprehensive screening and docking procedure identified several potential G6PD inhibitors. These compounds showed favorable interactions with the active site and met the criteria for optimal ADMET properties. The newly proposed G6PD inhibitors, with their potential to revolutionize cancer therapy, could serve as lead molecules for further research and development, inspiring the audience about the possibilities in cancer therapy.