RESUMEN
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.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Productos Biológicos/farmacología , Diterpenos/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Productos Biológicos/síntesis química , Productos Biológicos/química , Proliferación Celular/efectos de los fármacos , Diterpenos/síntesis química , Diterpenos/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
In addition to the known mulinolic and mulinenic acids, two diterpenoids, mulin-11-ene-13-alpha,14-alpha-dihydroxy-20-oic and mulin-12-ene-14-one-20-oic acids, were isolated from the aerial parts of Mulinum spinosum (Cav.) Pers. (Apiaceae). Their structures were determined based on spectroscopic studies.