RESUMO
The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.
Assuntos
Antineoplásicos/síntese química , Butadienos/síntese química , Carbazóis/síntese química , Maleimidas/química , Benzaldeídos/química , Hidrazinas/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Streptomyces/químicaRESUMO
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
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.
Assuntos
Antineoplásicos/síntese química , Lignanas/síntese química , Animais , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lignanas/farmacologia , Camundongos , Camundongos Endogâmicos DBA , Inibidores da Topoisomerase II , Células Tumorais CultivadasRESUMO
A new and versatile synthesis of combretastatins has been developed. Starting from commercially available materials, 2-phenyl-2-benzyl-1,3-dithianes were easily prepared and used as intermediates in the synthesis of several families of combretastatins. This approach facilitates the preparation of representative intermediates in a few steps, with or without an oxygenated function in the ethylenic residue. Many different analogues suitable for pharmacological evaluation can also be obtained from some of these intermediates.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Bibenzilas/síntese química , Estilbenos , Antineoplásicos Fitogênicos/química , Bibenzilas/química , Espectroscopia de Ressonância Magnética , Espectrofotometria UltravioletaRESUMO
Nine lignan derivatives (4-12) have been obtained from (-)-yatein by treatment with DDQ and NBS. They showed moderate antineoplastic activity (P-388, A-549, HT-29) compared with podophyllotoxin, but some of them have a better therapeutic index. None of the tested compounds shows anti-viral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activities.