RESUMO
Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35â µM. Proprotogracillin selectively inhibited A549 (IC50=0.58â µM) and A549/Taxol (IC50=0.74â µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40â µM.
Assuntos
Antineoplásicos Fitogênicos , Ensaios de Seleção de Medicamentos Antitumorais , Melanthiaceae , Rizoma , Saponinas , Espirostanos , Humanos , Saponinas/isolamento & purificação , Saponinas/farmacologia , Saponinas/química , Rizoma/química , Melanthiaceae/química , Espirostanos/química , Espirostanos/isolamento & purificação , Espirostanos/farmacologia , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Conformação Molecular , Relação Dose-Resposta a DrogaRESUMO
Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.