Cajamolides A-N: Cytotoxic and anti-inflammatory sesquiterpene lactones from Calea jamaicensis

Bioorg Chem. 2021 Nov:116:105351. doi: 10.1016/j.bioorg.2021.105351. Epub 2021 Sep 11.

Abstract

In the search for bioactive compounds from natural sources against cancer and inflammation, Calea jamaicensis (L.) L., a plant endemic to Panama, was investigated. Using multiple chromatographic steps, seventeen sesquiterpene lactones together with nine chromene derivatives were isolated from the non-polar extract of the plant. Among them, fourteen sesquiterpene lactones and three chromanes are described herein for the first time. Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. The isolated sesquiterpene lactones were tested against HeLa, SK-MEL-28 and HePG2 cancerous cell lines for their cytotoxic effects, as well as in the ICAM-1 assay for their anti-inflammatory potential. This study revealed strong cytotoxic agents on the one hand and strong inhibitors on the other. The compounds inhibited the TNF-α induced ICAM-1 expression on the endothelial HMEC-1 cells in a dose-dependent manner and with no toxicity observed on this non-cancerous cell line. In addition to the well-known cytotoxic activities of sesquiterpene lactones, further exploration may offer a novel therapeutic approach to cope with inflammatory diseases and the genus Calea may serve as a biobank for the isolation of potential phytopharmaceuticals, which could be utilized as leads in drug discovery and therapy.

Keywords: Anti-inflammatory; Asteraceae; Calea jamaicensis; Chromenes; Cytotoxicity; ICAM-1; MTT; Sesquiterpene lactones.

MeSH terms

  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Asteraceae / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Molecular Structure
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • ICAM1 protein, human
  • Lactones
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1