ABSTRACT
Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and can lead to serious complications such as nephropathy, neuropathy, retinopathy and cardiovascular disease. The aim of this work is to identify and investigate the inhibition mechanism of natural flavonoids and phenolics acids against, the α-amylase (αA) and α-glucosidase (αG). Therefore, we used different approaches; such as conceptual DFT and pharmacophore mapping in addition to molecular mechanics, dynamics and docking simulations. Whereas, a close agreement was found out to decide that Linarin (Flavones) provides more optimized inhibition of αA and αG enzymes. Our results have shown that Linarin could be useful as preventative agent, and possibly therapeutic modality for the treatment of metabolic diseases.Communicated by Ramaswamy H. Sarma.
Subject(s)
Diabetes Mellitus, Type 2 , Glycoside Hydrolase Inhibitors , Diabetes Mellitus, Type 2/drug therapy , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/therapeutic use , Humans , Molecular Docking Simulation , alpha-Amylases/metabolism , alpha-Glucosidases/metabolismABSTRACT
Five new unsaturated iridolactones 3-7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.