RESUMO
Approximately 60 derivatives of anguidin were prepared for evaluation of antitumor activities. Positions 3, 4, 8-10, and 15 were modified, and the resultant derivatives were screened against P-388 leukemia. It was found that introduction of the C3-keto and C3,C8-diketo groups markedly improved the antileukemic activity, whereas epoxidation of the C9-C10 double bond or oxidation of the C15 position diminished its activity. Selected derivatives were further tested in the L1210, B16, Lewis lung, Colon 36, and Colon 38 tumor lines. Among these compounds, 4 beta, 15-diacetoxyscirpene-3,8-dione (54) and 4 beta-(chloroacetoxy)-15-acetoxyscirpene-3,8-dione (55) were found to be most active in various tumors. Inhibitory action of several analogues on protein synthesis was also examined using H-HeLa cells.
Assuntos
Antineoplásicos/síntese química , Sesquiterpenos/síntese química , Tricotecenos/síntese química , Animais , Fenômenos Químicos , Química , Células HeLa/metabolismo , Humanos , Leucina/metabolismo , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Camundongos , Proteínas de Neoplasias/biossíntese , Neoplasias Experimentais/tratamento farmacológico , Relação Estrutura-Atividade , Tricotecenos/farmacologiaAssuntos
Antibacterianos/isolamento & purificação , Streptomyces/metabolismo , Estreptonigrina/análogos & derivados , Animais , Antibacterianos/farmacologia , Antibióticos Antineoplásicos/isolamento & purificação , Bactérias/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Leucemia P388/tratamento farmacológico , Camundongos , Streptomyces/classificação , Estreptonigrina/isolamento & purificação , Estreptonigrina/farmacologiaAssuntos
Aminoglicosídeos , Antibacterianos , Antibióticos Antineoplásicos/isolamento & purificação , Streptomyces/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Fenômenos Químicos , Química , Cumarínicos , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , CamundongosRESUMO
Six anthracycline antitumor agents, marcellomycin, musettamycin, rudolphomycin, alcindoromycin, collinemycin, and mimimycin, have now been isolated from bohemic acid complex. This has been achieved by classical column chromatography with Sephadex LH-20 and ammonia-neutralized silica and by analytical and prepatative hplc techniques with normal phase systems containing aqueous ammonia.
Assuntos
Antibacterianos/análise , Antibióticos Antineoplásicos/isolamento & purificação , Naftacenos/análise , Naftacenos/isolamento & purificação , Animais , Antraciclinas , Antibióticos Antineoplásicos/farmacologia , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Feminino , Leucemia L1210/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Camundongos , Testes de Sensibilidade Microbiana , Naftacenos/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Alcaloides de Pirrolizidina/isolamento & purificação , Alcaloides de Pirrolizidina/farmacologiaRESUMO
A series of derivatives of 5-methoxysterigmatocystin (3a,12c-dihydro-8-hydroxy-6,11-dimethoxy-7H-furol[3',2':4,5]furo[2,3-c]xanthen-7-one) has been prepared and evaluated for antitumor activity. The potency of the parent compound has been associated with the intact bisfurano ring system and with the double bond in the terminal furan ring. It has been shown that new substituents can be introduced in the xanthone portion of the molecule and that the antitumor activity is in some cases preserved.
Assuntos
Antineoplásicos/síntese química , Esterigmatocistina/síntese química , Xantenos/síntese química , Animais , Antineoplásicos/uso terapêutico , Leucemia Experimental/tratamento farmacológico , Camundongos , Esterigmatocistina/análogos & derivados , Esterigmatocistina/uso terapêutico , Relação Estrutura-AtividadeRESUMO
In a screening program for antitumor substances from microbial fermentations, a compound was isolated from the mycelium of an Aspergillus species which proved to be the mycotoxin 5-methoxysterigmatocystin. This and the subsequently isolated sterigmatocystin gave significant inhibition of the transplanted mouse leukemias P-388 and L-1210. Preparation and testing of several derivatives of 5-methoxysterigmatocystin suggest that certain functions in the molecule are essential for tumor inhibition. Although slight antitumor effects have been reported for the chemically related aflatoxins, we believe this is the first report of antitumor activity of sterigmatocystins.
