RESUMO
The preparation of new analogues of lignans carrying an imidazole ring has been achieved. Starting from L-histidinol, cis and trans stereoisomers have been obtained. The synthesized products lack the cytotoxicity displayed by related podophyllotoxins and azatoxin.
Assuntos
Lignanas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Humanos , Lignanas/síntese química , Piridinas/síntese química , Piridinas/farmacologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Two new indolocarbazole alkaloids, 4'-N-methyl-5'-hydroxystaurosporine (2) and 5'-hydroxystaurosporine (3), were isolated together with the known staurosporine (1) from the culture broth of a marine Micromonospora sp. (strain L-31-CLCO-002). The fermentation, structural data and cytotoxic activities of these compounds against various tumor cell lines are given.
Assuntos
Antineoplásicos/isolamento & purificação , Carbazóis/isolamento & purificação , Indóis/isolamento & purificação , Micromonospora/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carbazóis/química , Carbazóis/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Indóis/química , Indóis/farmacologia , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Camundongos , Micromonospora/crescimento & desenvolvimento , Micromonospora/metabolismo , Estaurosporina/análogos & derivados , Células Tumorais Cultivadas , Microbiologia da ÁguaRESUMO
Taking into account the structure of Combretastatins, we have synthesized and assayed for cytotoxic activity of new indole derivatives. Two aryl groups are maintained in the cis orientation required for activity by means of an indole moiety built up on less active ketoderivatives used as starting materials.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Bibenzilas/síntese química , Bibenzilas/farmacologia , Estilbenos , Antineoplásicos Fitogênicos/química , Bibenzilas/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células Tumorais CultivadasRESUMO
The hexane extract of aerial parts of Santolina rosmarinifolia subsp. canescens afforded eight new sesquiterpenes in addition to known compounds. Their structures were determined by spectroscopic methods and chemical transformations. The conformational analysis of the germacrane constituents was carried out by spectroscopic methods, including NMR at varying temperature and by molecular mechanics calculations. The antifeedant, antibacterial and antitumoral activity of selected compounds has been tested.
Assuntos
Asteraceae/química , Sesquiterpenos/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Células Tumorais CultivadasRESUMO
Several chloro- and iodo-lignanolides have been obtained by direct halogenation of aromatic rings from yatein and 4'-O-demethylyatein. They were assayed as antineoplastics, in order to check the influence in the activity of substitution in both aromatic rings. Although these compounds show a modest antineoplastic activity, it is far from that displayed by yatein and podophyllotoxin. These results confirm that demethylation and the introduction of halo substituents diminish the activity of lignans of the dibenzylbutyrolactone type.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Lignanas/síntese química , Lignanas/farmacologia , Animais , Antineoplásicos/química , Antivirais/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Lignanas/química , Estrutura Molecular , Células Tumorais CultivadasRESUMO
A new class of heteroaromatic analogs of lignans, called heterolignanolides, have been tested against several tumor cell lines. These compounds carry diverse heterocyclic rings, instead of the trimethoxyphenyl ring found in the natural lignans yatein and podorhizol. They have moderate antineoplastic activity (P-388, A-549, HT-29) compared with that of yatein. None of the tested compounds has discernible antiviral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activity.
