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.
Guillermo F Reta  1 ,  Alejandra I Chiaramello ,  Celina García ,  Leticia G León ,  Víctor S Martín ,  José M Padrón ,  Carlos E Tonn ,  Osvaldo J Donadel
Affiliations
  • 1. INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina.
PMID: 23831507 DOI: 10.1016/j.ejmech.2013.06.013
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.