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

RETA, GUILLERMO F.; CHIARAMELLO, ALEJANDRA I.; GARCÍA, CELINA; GONZALEZ LEON, LETICIA; MARTÍN, VICTOR S.; PADRÓN, JOSÉ M.; TONN, CARLOS E.; DONADEL, OSVALDO JUAN

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2013 vol. 2013 p. 28 - 38

0223-5234

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 labdanetype 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.