Virtual prediction of fava bean (Vicia faba L.) active compounds to inhibit G6PD enzyme activity

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary enzyme defect in humans, caused by a mutation in the X-linked gene encoding G6PD. The G6PD enzyme plays an important role to produced reducing agents which maintain reduced glutathione through pentose phosphate pathway. On ingestion of Faba Bean (Vicia faba L.), vicine and convicine are hydrolyzed by β -glucosidase to divicine and isouramil which can cause acute hemolytic anemia in patients with G6PD deficiency. This study aims to determine the molecular mechanism of bioactive compounds from fava beans as an inhibitor of the human G6PD Canton enzyme activity through an in silico approach. Screening for toxic bioactive compounds of V. faba was carried out using Swiss ADME. Molecular docking was performed to identify the interaction of divicine and isouramil binding with human G6PD Canton. Dobutamine hydrochloride was used as a negative control ligand. The result of Swiss ADME screening showed that convicine and vicine were not qualified for the Lipinski rules of five. Docking analysis demonstrated similar binding interaction of divicine and isouramil compared with control ligand to bound G6PD canton allosteric sites and shift the binding position of NADP+, suggesting these compounds interrupt the NADP+ to produce NADPH. The binding affinity of divicine (-7.0 kcal/mol) was lower than dobutamine hydrochloride (-6.9 kcal/mol), while isouramil was higher (-6.5 kcal/mol). Accordingly, this study was pointed out that divicine and isouramil have the potential as inhibitor of G6PD enzyme activity. Further, in vivo and in vitro studies are needed to confirm this research.