Details

Autor(en) / Beteiligte

• Reta, Guillermo F.
• Chiaramello, Alejandra I.
• García, Celina
• León, Leticia G.
• Martín, Víctor S.
• Padrón, José M.
• Tonn, Carlos E.
• Donadel, Osvaldo J.

Titel

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

Ist Teil von

• European journal of medicinal chemistry, 2013-09, Vol.67, p.28-38

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Syntheses of grindelic acid derivatives.•Oxy-nitrogenated and nitrogenated groups are key for the cytotoxic activity.•The more active derivative showed a GI50 values in the range 0.95–1.8 μM.•Labdanes-type diterpenes represent a potential source for new anticancer drug candidates.