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Advisor(s)
Abstract(s)
Diabetes mellitus is a non-infectious and non-transmissible life threatening disease. It is one of the
fastest growing health challenges of the current century, in which the number of adults living with
diabetes have more than tripled over the past 20 years. According to the International Diabetes
Federation, 1 in 11 adults (20-79 years) have diabetes (463 million people) and 2 in 3 people with
diabetes live in urban areas.1 This may be closely related to genetic and lifestyle factors such as
physical inactivity, unhealthy diets, obesity, raised blood cholesterol and glucose, stress, etc.2
Diabetes mellitus is an endocrine disorder that occurs when pancreas does not produce enough
insulin, when the body cannot use insulin efficiently or both situations, leading to chronic
hyperglycemia. Thus, the control of postprandial blood glucose level via the inhibition of digestive
enzymes, such as α-glucosidase and/or α-amylase, is a relevant strategy for the management of
type 2 diabetes and its complications.3
During the last two decades, in the pursuit for novel antidiabetic
drugs, a wide variety of natural and synthetic xanthone
derivatives have been applied in the inhibition of α-glucosidase
enzyme activity, however, the effects of this class of compounds
on the activity of α-amylase enzyme is scarce.4 With this ratio in
mind and as part of our on-going project, the aim of the present
study is to investigate the effect of a series of hydroxyxanthones 1
on pancreatic α-amylase activity to find out the relevance of this group of compounds in controlling
blood glucose levels for the treatment of disorders related with the carbohydrate uptake.
Different concentrations of xanthones 1 were incubated with the enzyme and the hydrolysis of
the substrate 2-chloro-p-nitrophenyl-α-D-maltotriose was monitored spectrophotometrically at 405
nm. Acarbose was used as the standard inhibitor. In addition, the study of the inhibition type was
carried out through nonlinear regression Michaelis-Menton enzymatic kinetics and the
corresponding Lineweaver-Burk plot.5
The results pointed out that the IC50 values obtained ranged from 23 to 90 μM, considerably
higher than the values obtained for the positive control acarbose (IC50 = 0.62 ± 0.07 μM). For the
active compounds, two of them revealed a competitive type of inhibition while for the remaining
ones a noncompetitive type of inhibition was recorded. More details concerning the structureactivity
relationship will be presented and discussed in this communication.
Description
Keywords
Diabetes Mellitus
Citation
Santos, Clementina M.M.; Proença, Carina; Freitas, Marisa; Araújo, Alberto N.; Silva, Artur; Fernandes, Eduarda (2020). Inhibition of pancreatic α-amylase activity by a group of hydroxyxanthones. In 13th National Organic Chemistry Meeting. Aveiro
Publisher
Sociedade Portuguesa de Química