Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis

Panpan Wu, Hao He, Hang Ma, Borong Tu, Jiahao Li, Shengzhu Guo, Silin Chen, Nana Cao, Wende Zheng, Xiaowen Tang, Dongli Li, Xuetao Xu, Xi Zheng, Zhaojun Sheng, Weiqian David Hong, Kun Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Research efforts have been directed to the development of oleanolic acid (OA) based α-glucosidase inhibitors and various OA derivatives showed improved anti-α-glucosidase activity. However, the inhibitory effects of indole infused OA derivatives on α-glucosidase is unknown. Herein, we synthesized a series of indole-OA (2a-2o) and -OA methyl ester (3a-3 l) derivatives with various electron withdrawing groups inducted to indole benzene ring and evaluated their anti-α-glucosidase activity. Indole OA derivatives (2a-2o) exhibited superior α-glucosidase inhibitory effects as compared to OA methyl ester derivatives (3a-3l) and OA (with IC50 values of 4.02 μM-5.30 μM v.s. over 10 μM and 5.52 µM, respectively). In addition, mechanistic studies using biochemical (kinetic assay), biophysical (circular dichroism), and computational (docking) methods revealed that OA-indole derivatives (2a and 2f) are mixed type of α-glucosidase inhibitors and their inhibitory effects were attributed to their capacity of forming the ligand-enzyme complex with α-glucosidase enzyme. Findings from this study support that OA indole derivatives are promising α-glucosidase inhibitors as a potential management of diabetes mellitus.

Original languageEnglish (US)
Article number104580
JournalBioorganic Chemistry
Volume107
DOIs
StatePublished - Feb 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Keywords

  • Antidiabetic
  • Benzene-ring-substituted indole
  • Circular dichroism
  • Docking
  • Oleanolic acid
  • α-glucosidase

Fingerprint Dive into the research topics of 'Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis'. Together they form a unique fingerprint.

Cite this