Flavonoids as alpha-glucosidase inhibitors: mechanistic approaches merged with enzyme kinetics and molecular modelling
- PDF / 595,624 Bytes
- 12 Pages / 547.087 x 737.008 pts Page_size
- 73 Downloads / 205 Views
(0123456789().,-volV) ( 01234567 89().,-volV)
Flavonoids as alpha-glucosidase inhibitors: mechanistic approaches merged with enzyme kinetics and molecular modelling Didem S¸ o¨hretog˘lu
. Suat Sari
Received: 8 February 2019 / Accepted: 21 May 2019 Ó Springer Nature B.V. 2019
Abstract Diabetes mellitus is a major, global public health problem. a-Glucosidase inhibitors are one of the most widely used classes of oral antidiabetics. In addition to other pharmaceutical benefits, flavonoids are known as potent a-glucosidase inhibitors. In the last two decades, the latter property of flavonoids has attracted a great interest. In the current review, the literature on flavonoids as inhibitors of a-glucosidase enzyme, their mechanism of action along with in silico studies and structure–activity relationships is discussed. The main outcomes show that a double bond between C-2 and C-3, and free hydroxyl groups at C-3 and C-40 are crucial. Whereas sugar substitution at any position on the aglycon reduced the inhibitory effect, a phenolic group like gallic acid, coumaric acid, etc. substituted at different positions of sugar units increased it. Hydroxylation of flavonoids generally enhanced the effect due to possible electrostatic interactions with the enzyme, making flavonols stronger inhibitors than their flavone analogues. Hydroxyl groups at C-3, C-7, ring B, and the carbonyl oxygen at C-4 are considered to be key modifications D. S¸ o¨hretog˘lu (&) Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Sıhhiye, 06100 Ankara, Turkey e-mail: [email protected] S. Sari Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, 06100 Ankara, Turkey
to enhance binding through hydrogen bonds. With this overview we intend to motivate and challenge researchers to design novel flavonoids a find new hits. Keywords a-Glucosidase Flavonol Flavone Isoflavone Molecular docking
Introduction Diabetes mellitus (DM), a chronic disease characterized by high blood glucose levels, stems from deficiencies in secretion of insulin, response to insulin, or both. Almost half a billion people have diabetes worldwide, and its prevalence is increasing continuously (IDF 2017). The chronic high blood glucose levels can cause severe complications, such as cardiovascular diseases, diabetic eye disease, nephropathy, diabetic foot, etc. Type 2 DM is the most common form of DM, accounting for more than 90% of all the cases (IDF 2017). Insulin injection or oral antidiabetic drugs are used for its treatment. aGlucosidase inhibitors are one of the most widely-used classes of oral antidiabetics today. The enzyme aglucosidase, located in the brush border of the enterocytes of the jejunum, catalyzes hydrolysis of dietary carbohydrates and converts them into monosaccharides, which are then absorbed in jejunum. Thus, a-glucosidase inhibitors delay glucose
123
Phytochem Rev
absorption and reduce postprandial blood glucose and insulin levels, hence alleviate hyperglycemia. Miglitol, acarbose, and v
Data Loading...
