RESUMEN
Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Fabaceae/química , Extractos Vegetales/farmacología , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/química , Inhibidores de Poli(ADP-Ribosa) Polimerasas/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Two new, aramatosides A and B (1 and 2), together with seven known oleanane-type triterpene saponins (3-9) were isolated from the leaves of Aralia armata. Their structures were determined by combination of HR-ESI-MS, 1 D and 2 D NMR spectral data as well as comparison with the previous literature. Compounds 6-9 exhibited cytotoxic effects towards three human cancer cell lines (HT29, A2058, and A549) with IC50 values ranging from 2.01 ± 0.17 to 18.8 ± 1.17 µM. Especially, compound 7 (narcissiflorin) showed significant cytotoxic activity against HT29 and A549 cell lines with IC50 values of 2.02 ± 1.65 and 2.01 ± 0.17 µM, respectively, which are smaller than those of positive control irinotecan hydrochloride (IC50 values of 10.3 ± 1.32 and 9.89 ± 0.19 µM).
Asunto(s)
Antineoplásicos Fitogénicos , Aralia , Ácido Oleanólico , Saponinas , Triterpenos , Antineoplásicos Fitogénicos/farmacología , Humanos , Estructura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Hojas de la Planta , Saponinas/farmacología , Triterpenos/farmacologíaRESUMEN
Three new triterpene saponins including two lupane-types and an ursane-type were isolated from the leaves of Trevesia palmata. Their structures were determined as 2α,3ß,23-trihydroxylup-20(29)-en-28-oic acid 3-O-α-L-arabinopyranoside (1), 2α,3ß,23-trihydroxylup-20(29)-en-28-oic acid 3-O-[α-L-arabinopyranoside]-28-O-[ß-D-glucopyranosyl] ester (2), and 2α,3ß,23-trihydroxyurs-12-en-28-oic acid 3-O-[α-L-arabinopyranoside]-28-O-[ß-D-glucopyranosyl(1â2)-ß-D-glucopyranosyl] ester (3) by analysis of their HR-ESI-MS, 1D and 2D NMR spectra. The 2α,3ß,23-trioxygenated pentacyclic triterpenes were uncommonly found in the nature. At concentration of 100 µM, compounds 1-3 inhibited NO production in LPS activated BV2 cells with inhibitory rates of 17.4 ± 1.8%, 33.1 ± 1.2%, and 11.7 ± 2.2%, respectively. But, they did not significantly inhibit yeast α-glucosidase activity.