Abstract:
Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired
insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms
of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic
drugs have therapeutic limitations, it is imperative to identify new potent inhibitors of natural product
origin which may slow carbohydrate digestion and absorption via alpha glucosidase. Since plant
extracts from Calotropis procera have been extensively used in the treatment of diabetes mellitus, the
present study used molecular docking and dynamics simulation techniques to screen its constituents
against the receptor alpha glucosidase. Taraxasterol, syriogenin, isorhamnetin-3-O-robinobioside
and calotoxin were identified as potential novel lead compounds with plausible binding energies of
-40.2, -35.1, -34.3 and -34.3 kJ/mol against alpha glucosidase, respectively. The residues Trp481,
Asp518, Leu677, Leu678 and Leu680 were identified as critical for binding and the compounds were
predicted as alpha glucosidase inhibitors. Structurally similar compounds with Tanimoto coefficients
greater than 0.7 were reported experimentally to be inhibitors of alpha glucosidase or antidiabetic.
The structures of the molecules may serve as templates for the design of novel inhibitors and warrant
in vitro assaying to corroborate their antidiabetic potential.
