Evaluation of in vitro anti-diabetic potential of 2, 3-diaryb(anthones through the inhibition of a-glucosidase

Type 2 diabetes mellitus is a chronic metabolic disorder caused by abnormal carbohydrate metabolism with a consequent hyperglycemia status, resulting from inadequate insulin secretion, action, or both. One possible therapeutic approach to decrease postprandial hyperglycemia is to retard the absorption of glucose via inhibition of carbohydrate hydrolyzing enzymes, such as a-glucosidase [l]. This enzyme catalyzes the final step of the digestive process of starch and break down oligosaccharides to monosaccharides. The currently marketed u-glucosidase inhibitors are confined to glycosidic compounds, such as acarbose, miglitol and voglibose, with moderate affinity for the enzyme and with disturbing side effects. Thus, in the last two decades, considerable interest hás been given to the pursuit ofnovel drugs, structurally diverse, in which several xanthone derivatives are induded [1, 2]. Our goal was to study the inhibitory activity of a panei of hydroxylated 2, 3-diarykanthones XH1-XH9, against of a-glucosidase activity. The in vitro assay was performed by monitoring the hydrolysis of the substrate p-nitrophenyl glucopyranoside into the product p-nitrophenol at 405 nm. In addiüon, the study of the inhibiüon type was carried out through nonlinear regression Michaelis-Menton enzymatic kinetics and the corresponding Lineweaver-Burk plot [3]. The IC^ values obtained ranged from 9 to 27 ^iM, considerably lower than the positive control"acarbose (IC = 515 ± 19 |iM). For the active compounds, a noncompetitive type inhibition was recorded. More details concerning the structure-activity relationship will be presented and discussed in this communication.This work received finandal support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/AGR/00690/2013; UID/QUI/50006/2013; UID/QUI/00062/2013, and "Programa Operacional Competitividade e Internacionalização" (COMPETE) (POC1-01-0145-FEDER-029241), and under the framework ofQREN (NORTE-01-0145-FEDER-000024).