Derivatives of grindelic acid: from a non-active natural diterpene to synthetic antitumor derivatives

Eur J Med Chem. 2013 Sep:67:28-38. doi: 10.1016/j.ejmech.2013.06.013. Epub 2013 Jun 18.

Abstract

Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (±0.38) μM against HBL-100 cells.

Keywords: 1,2,3-Triazole; Antitumor activity; Diamide derivatives; Labdane-type diterpenes; Multicomponent reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Proliferation / drug effects
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Biological Products
  • Diterpenes
  • grindelic acid