Synthesis Of Dihydroxylpentacyclic Triterpene Carboxylic Acid-nitrogen Heterocycle Derivatives And Their Study On α-glucosidase Inhibitory Activity In Vitro

In view of the principle of active splicing,the active unit 1-deoxynojirimycin and piperazines are bound to the C28 site of maslinic acid and corosolic acid by covalent bond to obtain twenty-two novel triterpenic acid derivatives.The structure of immediate compounds and target derivatives is characterized by ¹H/¹³C NMR and HRMS.Theα-glucosidase inhibitory activity of target derivatives is tested in the DMSO system and the preliminary structure-activity relationship of the compounds have been discussed.The results ofα-glucosidase inhibitory activity indicate most of the derivatives exhibit a certain inhibitory activity againstα-glucosidase.The inhibitory activity of triterpene-1-deoxynojirimycin derivatives varies significantly with the length of the carbon chain in the molecular structure.Compound 4a(IC₅₀=2041.4μM),4b(IC₅₀=1468.4μM),4c(IC₅₀=1718.4μM)and 5a(IC₅₀=1257.3μM)featuring the linker of alkyl chain（not exceeding 4carbon atoms）are show better inhibitory activity than those of their leading compound maslinic acid(IC₅₀=2540.6μM)and corosolic acid(IC₅₀=1363.7μM),respectively.However,with the longer hydrophobic carbon chain embedding the molecular structure,the inhibitory activity of the derivatives is lower than that of the parent compounds and the solubility of the derivatives is dropped.The piperazine segment of compounds with one free hydroxyl(12b:IC₅₀=499.6μM,13b:IC₅₀=660.7μM)and amino groups(12c:IC₅₀=768.5μM,13c:IC₅₀=819.2μM)present higher inhibition activity notably than that of maslinic acid and corosolic acid.It is worthy note that the hypoglycemic activity of compound 12b is superior to 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 K_i value is 570μM.The binding interaction between compounds withα-glucosidase are predicted by molecular docking simulation and the results demonstrate the active moiety 1-deoxynojirimycin in the molecules strengthen the hydrogen bonds withα-glucosidase and play an important role in improving the inhibitory activity of derivatives.