RESUMEN
A phytochemical investigation of the roots of Swietenia macrophylla led to the isolation of seven polyacetylenes, including five new compounds (1-5) and two known ones (6-7). Their structures were elucidated by extensive spectroscopic analysis and detailed comparison with reported data. All the isolates were tested for their cytotoxicity against the human hepatocellular carcinoma cell line BEL-7402, human myeloid leukemia cell line K562, and human gastric carcinoma cell line SGC-7901. Compounds 1 and 6 showed moderate cytotoxicity against the above three human cancer cell lines with IC50 values ranging from 14.3 to 45.4 µM. Compound 4 displayed cytotoxicity against the K562 and SGC-7901 cancer cell lines with IC50 values of 26.2 ± 0.4 and 21.9 ± 0.3 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Meliaceae/química , Raíces de Plantas/química , Polímero Poliacetilénico/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Células K562 , Polímero Poliacetilénico/químicaRESUMEN
Two new cardenolides, toxicarioside F (1) and toxicarioside G (2), were isolated from the latex of Antiaris toxicaria (Pers.) Lesch (Moraceae). Their structures were elucidated on the basis of spectral data and chemical evidence. Compounds 1 and 2 showed significant cytotoxicity against K562, SGC-7901, SMMC-7721, and HeLa cell lines in vitro by the MTT method.
Asunto(s)
Antiaris/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Glicósidos Cardíacos/aislamiento & purificación , Glicósidos Cardíacos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Glicósidos Cardíacos/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Células HeLa , Humanos , Células K562 , Látex/químicaRESUMEN
A new nor-cardenolide, named toxicarioside H (1), was isolated from the latex of Antiaris toxicaria (Pers.) Lesch (Moraceae). Its structure was elucidated on the basis of HRFAB-MS and spectroscopic techniques (IR, UV, 1D and 2D NMR). Compound 1 showed significant cytotoxicity against K562, SGC-7901, SMMC-7721, and HeLa cell lines in vitro by MTT method.
Asunto(s)
Antiaris/química , Cardenólidos/aislamiento & purificación , Cardenólidos/farmacología , Glicósidos Cardíacos/aislamiento & purificación , Glicósidos Cardíacos/farmacología , Látex/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Espectroscopía de Resonancia MagnéticaRESUMEN
Cytochalasin D targets actin and is ubiquitous in eukaryotic cells. When cytochalasin D is used as a cytotoxic agent in cancer therapy, it causes significant side effects. To prevent this, cytochalasin D can be encapsulated in polyethylene liposomes. In this study, high-performance liquid chromatography observation of the biodistribution of pegylated liposomal cytochalasin D in tumour-bearing mice showed that liposomal cytochalasin D could be conveniently dissolved in water for i.v. injection and that it specifically accumulated in tumour tissues, more than natural cytochalasin D did. The half-time of liposomal cytochalasin D in the plasma was also significantly longer than that of natural cytochalasin D (4h versus 10 min). MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that liposomal cytochalasin D treatment could cause significant inhibition of cell proliferation in vitro in a manner similar to that of natural cytochalasin D. The antitumour activities of liposomal cytochalasin D were investigated in B16 melanoma, CT26 colorectal carcinoma and H22 hepatoma models, and the results indicated that liposomal cytochalasin D could significantly inhibit tumour growth and prolong survival in a manner similar to that of cisplatin. TUNEL-based apoptosis assays showed that liposomal cytochalasin D induced significant tumour cell apoptosis. Significant inhibition of tumour angiogenesis was observed in mice treated with liposomal cytochalasin D. In addition, no significant side effects were observed in mice treated with liposomal cytochalasin D. Our results show that liposomal cytochalasin D increases solubility and bioavailability, a lower incidence of side effects and improves antitumour effects, indicating its potential as a chemical agent for cancer therapy.