Chinese Journal of Organic Chemistry >
Structural Modification of Benzimidazole-Iminosugars and Their Inhibitory Activities against β-Glycosidases
Received date: 2021-05-02
Revised date: 2021-05-31
Online published: 2021-06-22
Supported by
National Natural Science Foundation of China(21772031); Natural Science Foundation of Hebei Province(B2019201398)
The benzimidazole-fused tricyclic iminosugars 1 and 2 derived from D-ribose inhibited β-glucosidase significantly. On the basis of the structural modification on the phenyl ring of 1 and 2, thirty novel tricyclic iminosugars 11a~11g, 12a~12g, 13a~13h and 14a~14h bearing mono-substituent on the different positions on phenyl ring were synthesized through Mitsunobu reaction. The inhibitory activities of newly synthesized compounds were tested against β-glucosidase (almonds). The results showed that compound 13e and the mixture of 13f and 14f exhibited significantly β-glucosidase inhibitory activities with IC50 values of 0.49 and 0.25 μmol/L, respectively, higher than that of the positive control, miglitol. The analysis of structure activity relationship (SAR) suggested that six-membered iminosugar ring in such fused tricyclic iminosugars was on the benefit of the compounds against β-glucosidase. The electron donor group on the 3' or 4' positions on the phenyl ring, such as methyl or methoxyl, would greatly promote the β-glucosidase inhibitory activities of the inhibitors.
Fengxing Li , Xin Lu , Xu Liu , Lulu Su , Xiaoliu Li , Hua Chen . Structural Modification of Benzimidazole-Iminosugars and Their Inhibitory Activities against β-Glycosidases[J]. Chinese Journal of Organic Chemistry, 2021 , 41(9) : 3643 -3651 . DOI: 10.6023/cjoc202105003
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