One-pot three steps cascade synthesis of novel isoandrographolide analogues and their cytotoxic activity

Eur J Med Chem. 2017 Sep 29:138:952-963. doi: 10.1016/j.ejmech.2017.07.035. Epub 2017 Jul 21.

Abstract

An efficient one-pot synthesis of novel andrographolide analogues is reported from a naturally occurring and abundant andrographolide isolated from aerial parts of Andrographis paniculata. Reactions in the one-pot proceed through a cascade epoxide ring opening by aniline derivatives/intramolecular ring closing and oxa-conjugate addition-elimination reactions. This methodology produces a new series of 17-amino-8-epi-isoandrographolide analogues in fair to excellent yields with high stereoselectivity using an economic and environmental procedure without base or catalyst at room temperature. Twenty-five analogues were obtained and cytotoxicity of all new analogues were evaluated against six cancer cell lines to search for a new lead compound based on andrographolide structure.

Keywords: Andrographis paniculata; Cytotoxic activity; Epiandrographolide.

MeSH terms

  • Andrographis / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Diterpenes
  • andrographolide