Trans-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase

Abstract

Trans-chalcone (1,3-diphenyl-2-propen-1-one), a biphenolic core structure of flavonoids precursor was tested for inhibitory activity toward alpha-amylase. Porcine pancreatic alpha-amylase was observed to be effectively inhibited by this compound, which showed competitive behavior with a K(i) of 48 μM. Soluble starch (the natural substrate of the enzyme) was used in this study in order to obtain more realistic results. The possible binding mode of the compound was assessed in silico, and the two residues Trp59, and Tyr62 were proposed as main interacting residues with trans-chalcone. In conclusion, this compound could be used to design effective inhibitors of alpha-amylase.

The Effect of Aspalathin on Levels of Sugar and Lipids in Streptozotocin-Induced Diabetic and Normal Rats

“…With drawing Dixon plot it was determined that Ki of aspalathin on alpha amylase is 37.0 µM (Figure 2). The result of this study, the same as other our previous study on trans-chalcone (Ki = 48 µM) and curcumin (20.17 µM) showed that these compound are nearly highly potent inhibitor for alpha amylase activity [3,11,17,18]. As mentioned before, new diabetic therapies seek ways to affect multiple targets at the same time with consideration of fewer side effects [27][28][29][30].…”

“…Besides, administration of aspalathin at different doses resulted in the correction of lipid profile. The general results of this study are the same as our previos study, the effect of flavonoids such as chalcone and curcumin on levels of sugar and lipids [3,11,17,18]. As shown in Figures 3 and 4, a decrease in glycemia was occurred after aspalathin administration in all the doses used in diabetic and normal rats.…”

“…Classical inhibitors of mammalian α-amylase include protein and carbohydrate like structures, the latter mainly based on acarbose [24]. In recent years, small molecules have also been studied in this regard, and among these flavonoids have been reported to exhibit such activity similar to our previous experience on trans-chalcone and curcomin [3,11,17,18]. The aim of this research was to study the inhibitory effect of aspalathin, a chalcone derivative on alpha amylase activity and effect of this compound on levels of sugar and lipids in diabetic and normal rats.…”

“…Remaining activity was calculated as a percentage by comparison with the control sample activity, the activity of enzyme in presence of DMSO. All experiments were done at least three times and average values reported [16,17].…”

Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice

“…Trans-chalcone structure is a precursor to flavonoids and chalcone compounds and possess a range of therapeutic properties including an-tioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory (12). We had previously observed the alpha-amylase inhibitory effect of trans-chalcone in vitro (13), and its beneficial effect on streptozotocin-induced diabetic mice (14).…”