Marisa Freitas
University of Porto, Portugal
Title: Prediction of anti-diabetic activity of flavonoids targeting α-glucosidase
Biography
Biography: Marisa Freitas
Abstract
The limitations of currently available oral antidiabetic agents in what concerns the efficacy/safety, together with the global development of the diabetes, have stimulated the scientific community to find alternative therapies. The inhibition of α-glucosidase, the most important enzyme in the gut for the breakdown of carbohydrates before monosaccharides absorption, has been recognized as the most effective measure in reducing post-prandial hyperglycemia (PPHG) from all available antidiabetic drugs. Some flavonoids, have been shown to exhibit inhibitory effects against α-glucosidase enzymes. Nevertheless, the information found in the literature is disperse and variable, thus hindering comparisons and consequently conclusions about their efficacy against α-glucosidase activity. Thus, our aim was to establish a structure - activity relationship of a panel
of flavonoids against α-glucosidase activity, covering a solid set of different structures. The evaluation of α-glucosidase activity was performed in vitro by monitoring the α-glucosidase-mediated transformation of the substrate p-nitrophenyl-α-Dglucopyranoside (pNPG) into into p-nitrophenol. The inhibitory kinetic analysis was made by using nonlinear regression Michaelis-Menten enzyme kinetics and the corresponding Lineweaver-Burk plot. We concluded that the flavonoid structure, and the position and number of OH groups are determinant factors for the intended effect. The most active compound was quercetin, showing a competitive inhibition, which indicates that hydroxylation at 3, 5, 7 positions of the A-ring and at 3’ and 4’ positions of the B-ring, as well as the 2,3 double bond in the C-ring, are important for the inhibitory activity of flavonoids.