RESUMO
BACKGROUND: The conjugates of the sesquiterpene lactone of the eremophilane series of 6- hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer. OBJECTIVE: A lactone with an unusual skeleton "6-hydroxyxanthanodiene" was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer. METHODS: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms. RESULTS: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 µM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 µM) without any toxic side effect on healthy cells. CONCLUSION: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Inula/química , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Células A549 , Animais , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Concentração Inibidora 50 , Células Jurkat , Lactonas/química , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Sesquiterpenos/químicaRESUMO
BACKGROUND: Oxidative stress and amyloid deposition are tightly interconnected pathological features of Alzheimer disease. In this respect, both amyloid production and aggregation may be stimulated by oxidative stress and also the increase of pathogenic ß-amyloid and its aggregated form lead to oxidative stress progression. Therefore, the search for potential drugs with both antioxidant and antiaggregation properties are of great interest. METHODS: In this study, we described the stereospecific synthesis of alkaloid securinine aminoderivatives. RESULTS: We showed that the newly synthesized compounds possess antioxidant and metal-chelating properties. Indeed, we report that one compound has inhibitory effects towards µ-amyloid aggregation. CONCLUSION: Based on these results, aminoderivatives of securinine scaffold are promising compounds for development of new drugs for the treatment of neurodegenerative diseases.