Preparation and α -glucosidase inhibition of andrographolide derivatives

AbstractSeries of novel analogs, which were primarily modified on its lactone moiety, was synthesized based on Andrographolide (1), a natural product sesquiterpene inhibitor ofα-glucosidase. Among new analogs, 14-deoxy-11,12-didehydro-15-(4-ethoxybenzylidene)andrographolide (3h) was determined to have the greatest potential ofα-glucosidase inhibitor through the calculation of IC50 value of 160  ± 5.1 μM, a significant improvement compared to the clinical dose of Acarbose, which showed the IC50 value of 390  ± 8.1 μM. In addition, 14-deoxy-11,12-didehydro-3,19-(2′-hydroxybenzylidene)-15-(2-hydroxybenzylidene) andrographolide (7), a 15-benzylidene derivative of 14-deoxy-11,12-didehydroandrographolide containing a 1,3-dioxane moiety at C(3) and C(19), also displayed good inhibition with IC50 260  ± 13 μM. These results are promising avenues in the subsequent optimization of antidiabetic drugs.

Source: Medicinal Chemistry Research - August 16, 2020 Category: Chemistry Source Type: research