Identification and screening of potential inhibitors obtained from Plumeria rubra L. compounds against type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is the inability of the body's cells to retaliate to insulin, which can periodically culminate into absolute insulin deficiency. Hyperinsulinemia can be alleviated by administering oral medications or insulin. Prevailing medicaments engender repercussions with prolonged use, as they transmute to an inefficacious form. Hence, it will be advantageous to design plant-derived antihyperglycemic drugs with remarkable efficacy and safety quotients to address T2DM and associated comorbidities. Based on prior research, we have identified 7 novel phytocompounds from Plumeria rubra L. and 5 co-crystals that serve as an important residence for T2DM. The compounds are assessed for their inhibitory activity and dynamic stability against five major receptors which are responsible for T2DM. Additionally, in silico ADMET assessment followed by GPU-enabled GROMACS was performed on the selected compounds. The results demonstrated that β-d-Hexaglucoside had the highest binding affinity, hydrophobicity and bond length in contrast to all the targeted receptors. β-d-Hexaglucoside was subjected to dynamic simulation to analyze the root mean square deviation and root mean square fluctuation graph rates using the GROMOS force field in GROMACS software. Furthermore, β-d-Hexaglucoside exhibited inhibitory activity against diabetic receptors with a docking score of -9.5 kcal/mol. The current study proposes β-d-Hexaglucoside as a potential candidate for in-vitro or pre-clinical investigations to ameliorate T2DM management. Communicated by Ramaswamy H. Sarma.