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