Molecular Structure-Based Screening of the Constituents of Calotropis procera Identifies Potential Inhibitors of Diabetes Mellitus Target Alpha Glucosidase

Current Issues in Molecular Biology

Daniel Boison¹  Issaka Obuaba¹  Russell Koranteng²  Cynthia A. Adinortey³  Michael D. Wilson⁴  Gabriel B. Kwarko⁵  Samuel K. Kwofie⁵ 

[1] Department of Biochemistry, School of Biological Sciences, University of Cape Coast, Cape Coast CC 033, Ghana;Department of Biomedical Engineering, School of Engineering Sciences, College of Basic & Applied Sciences, University of Ghana, Legon, Accra LG 77, Ghana;Department of Molecular Biology and Biotechnology, School of Biological Sciences, University of Cape Coast, Cape Coast CC 033, Ghana;Department of Parasitology, Noguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences (CHS), University of Ghana, Legon, Accra LG 581, Ghana;West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Accra LG 54, Ghana;

关键词: diabetes;    Calotropis procera;    alpha glucosidase;    cheminformatics;    molecular docking;    molecular dynamics simulations;   

DOI  :  10.3390/cimb44020064

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown