1. Semi-synthesis of C28-modified triterpene acid derivatives from maslinic acid or corosolic acid as potential α-glucosidase inhibitors.
- Author
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Liu, Xiaoqin, Zang, Xufeng, Yin, Xiaoli, Yang, Wuying, Huang, Jinxiang, Huang, Jianping, Yu, Chunxian, Ke, Chunshan, and Hong, Yanping
- Subjects
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GLUCOSIDASES , *ACID derivatives , *PIPERAZINE , *CARBOXYLIC acid derivatives , *MOLECULAR docking , *ENZYME kinetics , *COVALENT bonds - Abstract
Two series of pentacyclic dihydroxyterpene carboxylic acid derivatives were synthesized via introduction of saturated nitrogen heterocycle segments (i.e. 1-DNJ and piperazines) at C28 site in MA and CA. Some of the compounds exhibited a better α-glucosidase inhibitory activity than those of precursors and positive compound (acarbose) in the DMSO measurement system. Simultaneously, kinetics study and molecule docking were carried on the active compounds. • MA / CA coupled with 1-deoxynojirimycin (or piperazines) were synthesized. • α-Glucosidase inhibitory activities of the derivatives were evaluated in vitro. • Eight derivatives presented higher inhibitory activity than that of precursors. • Compound 12b exhibited a better inhibitory than that of precursors and acarbose. 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 : IC 50 = 1468.4 µM; 12b : IC 50 = 499.6 µM 12c : IC 50 = 768.5 µM, 13c : IC 50 = 819.2 µM) show superior inhibitory activity in α-glucosidase than that of the precursor maslinic acid (IC 50 = 2540.6 µM) or corosolic acid (IC 50 = 1363.7 µM), in which compound 12b (IC 50 = 499.6 µM) possesses stronger inhibitory activity than that of acarbose (IC 50 = 606 µM). 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 K i is 570 µM. The binding interaction between compounds with α-glucosidase are predicted by molecular docking simulation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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