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Eighteen derivatives of pentacyclic triterpene carboxylic acids including Maslinic acid (MA), Corosolic acid (CA) and Asiatic acid (AA) have been synthesized by coupling the piperazine- l -amino acid complex at the C-28 site of the parent compounds. The results of α-glucosidase inhibitory activity in vitro indicate that two compounds 15e and 16e are closed to that of the reference acarbose in ethanol-water system. Besides, compound 16e shows superior inhibitory activity than acarbose in the DMSO system. Simultaneously, enzyme kinetics has been revealed. [Display omitted] • MA / CA / AA integrated with piperazine- l -amino acid complex have been synthesized. • α-Glucosidase inhibitory activity of pristine derivatives was evaluated in vitro. • The IC 50 value of two compounds is near to that of acarbose in ethanol-water system. • A compound achieves higher inhibitory activity than acarbose in DMSO. • Structure-activity relationship (SAR) of derivatives is also discussed. Eighteen derivatives of pentacyclic triterpene carboxylic acids (Maslinic acid, Corosolic acid and Asiatic acid) have been prepared by coupling the piperazine complex of l -amino acids at the C-28 site of the parent compounds. The α-glucosidase inhibitory activities of the pristine derivatives were evaluated in vitro. The results indicated that the inhibitory activity of some compounds (15e IC 50 = 591 μM, 16e IC 50 = 423 μM) was closed to that of the reference acarbose (IC 50 = 347 μM) in ethanol-water system. In addition, compound 16e (IC 50 = 380 μM) showed superior inhibitory activity than acarbose (IC 50 = 493 μM) in the measurement system with DMSO as solvent. The comparison of two different solvent systems showed that the derivatives had better α-glucosidase inhibitory activity in the DMSO system than that of in ethanol-water system. Regrettably, all of the as-synthesized derivatives exhibited inferior α-glucosidase inhibitory activities than those of the parent compounds in both test solvent systems. Furthermore, the result of enzyme kinetics demonstrated that the inhibition mechanism of compound 16e was noncompetitive inhibition with the inhibition constant K i = 552 μM. [ABSTRACT FROM AUTHOR]

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]