Virtual screening and molecular docking of red Acalypha wilkesiana leaf extract-derived compounds as SGLT2 inhibitors for Type 2 diabetes therapy

Abstract

Diabetes mellitus is a hullmark of metabolic disorder, a life – threatening condition that affect millions of individuals globally. Ethno-medicinal and scientific reports abound on the use of Acalypha wilkesiana leaf extract in managing diabetic patients. This study employed gas chromatography-mass spectrometry (GC-MS) and computational approach to investigate the phytochemical profile and potential bioactive properties of A. wilkesiana leaf. GC-MS analysis revealed distinct variations in phytochemical composition ranging from monoterpenes, sesquiterpenes, alkaloids etc,hence identify and validate hit compounds from the crude leaf extract with the potential to inhibit SGLT-2 receptor. Molecular docking results showed that the binding affinity of the hit molecule indazol-4-one, 3,6,6-trimethyl-1-phthalazin-1-yl-1,5,6,7-tetrahydro- (-10.7 kcal/mol) was very close to the control drug Sotagliflozin (–11.4 kcal /mol) at this target. ADMET analysis predicted that the properties of these compounds were within acceptable limits with the hit molecule showing better druglikeness than the conventional drug used as control. These results indicate that A. wilkesiana holds promise as a therapeutic agent for the management of diabetes, warranting further investigation into its therapeutic potential.