RESUMO
Nine tropane alkaloid aromatic esters (1-9) were isolated from the roots of Erythroxylum pervillei by following their potential to reverse multidrug-resistance with vinblastine-resistant oral epidermoid carcinoma (KB-V1) cells. All isolates, including seven new structures (3-9), were evaluated against a panel of human cancer cell lines, and it was found that alkaloids 3 and 5-9 showed the greatest activity with KB-V1 cells assessed in the presence of vinblastine, suggesting that these new compounds are potent modulators of P-glycoprotein. Confirmatory results were obtained with human ovarian adenocarcinoma (SKVLB) cells evaluated in the presence of adriamycin and synergistic studies performed with several cell lines from the NCI tumor panel. The structures of the new compounds were determined using spectroscopic techniques. Single-crystal X-ray analysis was performed on the monoester, tropane-3 alpha,6 beta,7 beta-triol 3-phenylacetate (1).
Assuntos
Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Erythroxylaceae/química , Plantas Medicinais/química , Tropanos/isolamento & purificação , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/química , Ésteres/isolamento & purificação , Ésteres/farmacologia , Feminino , Humanos , Madagáscar , Medicina Tradicional , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Neoplasias Ovarianas , Raízes de Plantas/química , Espectrofotometria Infravermelho , Estereoisomerismo , Tropanos/química , Tropanos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.