In-Silico Computational Study of Polyhydroxylated Nortropane Alkaloid from Kangkong (Ipomoea aquatica) as a Potential Αlpha-Glucosidase Inhibitor for Possible Blood Sugar Reduction via Molecular Docking

Abstract

This study, In-silico computational study of polyhydroxylated nortropane alkaloid from kangkong (Ipomoea aquatica) as a potential αlpha-glucosidase Inhibitor for possible blood sugar reduction via molecular docking, investigated polyhydroxylated nortropane alkaloids from Kangkong (Ipomoea aquatica) as potential α-glucosidase inhibitors for blood sugar reduction using molecular docking. Calystegine derivatives (A3, B1, B2, B3, B4, and C1) were docked against N-terminal maltase-glucoamylase (NtMGAM), C-terminal maltase-glucoamylase (CtMGAM), and N-terminal sucrase-isomaltase (NTSI) enzymes, with acarbose as the reference inhibitor. All ligands exhibited negative binding affinities, indicating stable and energetically favorable interactions. Among the derivatives, Calystegine B4 demonstrated the highest binding affinities across all targets (−6.9 kcal/mol for NtMGAM, −6.6 kcal/mol for CtMGAM, and −6.7 kcal/mol for NTSI), followed by B1 and B3, while A3, B2, and C1 exhibited moderate to low interactions. The binding energies of the calystegines were comparable to that of acarbose. Interaction analyses revealed that calystegines bind within the catalytic sites through hydrogen bonding and van der Waals interactions, suggesting a competitive inhibition mechanism. These findings identify Calystegine B4 and B1 as the most promising candidates and support the potential application of calystegine derivatives as natural α-glucosidase inhibitors for regulating post-meal blood glucose levels.