Cheminformatics identification of modulators of key carbohydrate-metabolizing enzymes from C. cujete for type-2 diabetes mellitus intervention

Abstract Purpose The therapeutic use of oral hypoglycaemic agents in the management type-2 diabetes mellitus (T2DM) is without adverse effects; thus, calls for alternative and novel candidates from natural products medicinal plants. Method study explored molecular docking dynamics (MD) simulation approaches to identify key antidiabetic metabolites Crescentia cujete . Results Molecular results identified four and/or five best compounds against each target enzyme (alpha-glucosidase, dipeptidyl peptidase-IV, aldose reductase, protein tyrosine phosphatase-1B (PTP-1B)) implicated diabetes. resulting complexes (except PTP-1B) had higher scores above respective standards (acarbose, Diprotin A, ranirestat). MD revealed such as benzoic acid (-48.414 kcal/mol) phytol (-45.112 well chlorogenic (-42.978 naringenin (-31.292 binding affinities than [acarbose (-28.248 kcal/mol), ranirestat (-21.042 kcal/mol)] alpha-glucosidase respectively while A ursolic (-18.740 presented superior [luteolin (-41.957 kcal/mol (-16.518 DPP-IV PTP-1B respectively. Conclusion While isoflavone (alpha-glucosidase), xylocaine (DPP-IV), luteolin (aldose reductase,) (PTP-1B) were affirmed inhibitors targets, luteolin, may be suggested proposed probable T2DM related retinopathy complication based on their structural stability, compactness affinity three (DPP-IV, targets investigated. Further studies are warranted vitro vivo antihyperglycaemic effects these drug candidates.