Semi-synthesis of C28-modified triterpene acid derivatives from maslinic acid or corosolic acid as potential α-glucosidase inhibitors.

Abstract

Combining two bioactive moieties by covalent bond into a novel single hybrid biological entity in view of the principle of active splicing, twenty-two C28-modified derivatives of pentacyclic dihydroxytriterpene carboxylic acids with saturated nitrogen heterocycle segments (i.e. 1-deoxynojirimycin or piperazines) have been synthesized. The inhibitory activities of all final target compounds on α-glucosidase were evaluated in vitro. The results of α-glucosidase inhibition assay indicate that some derivatives (e.g. 4b: IC50=1468.4µM; 12b: IC50=499.6µM 12c: IC50=768.5µM, 13c: IC50=819.2µM) show superior inhibitory activity in α-glucosidase than that of the precursor maslinic acid (IC50=2540.6µM) or corosolic acid (IC50=1363.7µM), in which compound 12b (IC50=499.6µM) possesses stronger inhibitory activity than that of acarbose (IC50=606µM). In addition, the result of enzyme kinetics study reveals that the inhibitory mechanism of the compound 12b is non-competitive inhibition and the inhibition constant Ki is 570µM. The binding interaction between compounds with α-glucosidase are predicted by molecular docking simulation.