New α-glucosidase inhibitors from a chemically engineered essential oil of Origanum vulgare L.

Abstract

Chemical transformation of plant extracts can lead to the generation of semisynthetic derivatives that display biomolecular properties that were absent in the natural components of the starting material. The objective of this work was to produce new α-glucosidase inhibitors through O-sulfonylation of essential oils. Thirteen essential oils were chemically diversified with benzenesulfonyl chloride and screened for their in vitro α-glucosidase inhibitory effect. The chemically engineered Origanum vulgare L. (Lamiaceae) essential oil showed the highest inhibition percentage of the series. Using chromatography, nuclear magnetic resonance, and mass spectrometry, the benzenesulfonyl esters of thymol and carvacrol were identified as responsible compounds for the observed α-glucosidase inhibition. Therefore, a series of twelve arylsulfonyl esters of carvacrol and thymol was prepared. These compounds showed interesting physicochemical properties in silico. Their α-glucosidase inhibition evaluation revealed three compounds with half maximal inhibitory concentration values in the low micromolar range (≅ 2.5 μM), i.e., fifty times more active than acarbose. These compounds showed good selectivity for α-glucosidase compared with α-amylase, β-glucosidase, and β-galactosidase. The two most potent compounds, 7 and 8, are reversible and mixed type α-glucosidase inhibitors. The results indicate that the directed chemical transformation of essential oils can be a useful strategy to discover new α-glucosidase inhibitors.