Synthesis of norisoboldine derivatives and bioactivity assay for inducing the generation of regulatory T cells

Bioorg Med Chem Lett. 2021 Apr 1:37:127844. doi: 10.1016/j.bmcl.2021.127844. Epub 2021 Feb 5.

Abstract

In this study, we used chemical modification to improve the pharmacological activity of norisoboldine (NOR). A new NOR-benzoic acid derivative, named DC-01, showed more potent induction of Treg cell differentiation than NOR. The in vitro effective concentration of DC-01 (1 μM) is about an order of magnitude lower than that of NOR (10 μM). DC-01 (28, 56 mg/kg) showed better amelioration of dextran sodium sulfate-induced colitis in mice than NOR (20, 40 mg/kg), and DC-01 (28 mg/kg) increased the number of Treg cells slightly better than NOR (20 mg/kg). In summary, DC-01 exerts more potent induction of Treg cell generation, which might be a candidate drug for the treatment of inflammation- and immune-related diseases.

Keywords: Derivatives; Norisoboldine; Regulatory T cells; Structural modification; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Survival
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Dextran Sulfate
  • Dose-Response Relationship, Drug
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship
  • T-Lymphocytes, Regulatory / drug effects*
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • norisoboldine
  • Dextran Sulfate