RESUMEN
In our search for neuroprotective agents, six previously undescribed highly oxidized guaiane sesquiterpenes, linderaggrols A-F (1-6), together with three known sesquiterpenes, were isolated from the roots of Lindera aggregata (Sims) Kosterm. Their structures including absolute configurations were established by a combination of NMR spectroscopic techniques and single crystal X-ray diffraction experiments. Compounds 1-6 represented the first instances of guaiane 12(8),15(6)-dilactones. Additionally, compound 6 possessed a rare 1,8-O-bridge. Neuroprotective effects against erastin-induced ferroptosis on HT-22 cells showed that some compounds demonstrated neuroprotective effects at 20.0 µM.
Asunto(s)
Lindera , Fármacos Neuroprotectores , Raíces de Plantas , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Raíces de Plantas/química , Lindera/química , Estructura Molecular , Oxidación-Reducción , Sesquiterpenos de Guayano/química , Sesquiterpenos de Guayano/farmacología , Sesquiterpenos de Guayano/aislamiento & purificación , Ratones , Lactonas/farmacología , Lactonas/química , Lactonas/aislamiento & purificación , Animales , Supervivencia Celular/efectos de los fármacos , Línea Celular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Modelos MolecularesRESUMEN
A serial jatrophane-type diterpenoids, comprised with three undescribed compounds kanesulones C-E (1-3) and four known ones (4-7), were obtained from the roots of Euphorbia kansui. The structures of compounds 1-3 were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS, the absolute configuration of 1 was revealed by single crystal X-ray diffraction. These isolates were assayed for their multidrug resistance reversing activities on human breast adenocarcinoma cell line MCF-7/ADR. Compound 1 possessed potential as low toxic MDR modulator that could promote the efficacy of anticancer drug adriamycin ca. 85-fold at 5â µM, as 12â times stronger than the positive drug verapamil.