Strategies in the Design of Antidiabetic Drugs from <em>Terminalia Chebula Retz.</em> Using <em>in silico</em> and <em>in vitro</em> Approach

Abstract

Diabetes mellitus is the fifth deadliest disease in the developing countries. Even with all the research and new drugs available, combating diabetes is still challenging. There are successes in finding new cost effective drugs without side effects, even if not perfect. In our investigation we studied binding mechanism of secondary metabolite of T. chebula in silico. It was observed that three compounds out of 16 have a higher binding affinity for the target proteins. Ellagic acid showed highest binding affinity with alpha amylase, beta glucosidase and alpha glucosidase with lesser binding energies -4.5kcal/mol, -5.36kcal/mol and -4.48kcal/mol respectively. Arjungenin has lesser binding energy of 4.77 kcal/mol with glucokinase while luteoline has binding energy of -7.25kcal/mol for enzyme glycogen synthase kinase. These entire compounds interacted with non-covalent interaction. Petroleum ether extract showed the significant alpha amylase inhibitory activity i.e. 51.22% as compared to standard drug (65.99%).TLC analysis revealed the presence of total 9 compounds in different plant extracts one of them might be a lead compound which could be further exploited for the development of novel safer and potent antidiabetic drug.

Flavonoids as Human Intestinal α-Glucosidase Inhibitors

“…At the molecular level, the binding between hydroxyls in ring A, B or C of flavonoids to the active sites of α-glucosidases leads to structural changes in the enzyme evidenced by several docking studies with yeast α-glucosidase [20,55,72,79]. The inhibitory activity of flavonoids was concluded to be in the decreasing order of anthocyanidin ≥ isoflavone ≥ flavonol ≥ flavone ≥ flavonone ≥ flavan-3-ol [50], indicating the crucial role of A ring hydroxylation for potent α-glucosidases inhibition [80].…”

A systematic review of the inhibitory effect of extracts from edible parts of nuts on α-glucosidase activity

“…7 Certain flavonoids attenuate the activity of digestive enzymes 7,11 and are the major polyphenol class in nuts. 43 Data on the yeast α-glucosidase indicates that binding of the hydroxyl groups in ring A, B or C of flavonoids to the active sites of α-glucosidases results in subtle modifications of the enzyme structure [44][45][46][47] and inhibition is increased by hydroxylation of the A ring at the C5 or C6 of flavonoids. 11,48,49 To ensure that we captured all papers on nut extracts and inhibition of α-glucosidase activity, we performed a systematic review of the literature.…”