RESUMO
As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed high potency in the P388 leukemia assay. 4-Hydroxy analogue 4d showed the most potent activity (T/C = 195%) at a 5 mg/kg dose. The introduction of large-size substituents, of which the steric influence prevents coplanarity of the substituted aromatic function, resulted in a remarkable decrease in the potency. X-ray structural analysis of highly potent 4-methoxy analogue 4b was undertaken.
Assuntos
Antineoplásicos , Cicloeptanos/síntese química , Tropolona/síntese química , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Indicadores e Reagentes , Células KB , Leucemia P388/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Relação Estrutura-Atividade , Tropolona/análogos & derivados , Tropolona/uso terapêuticoRESUMO
Treatment of tropolones with benzaldehyde diethyl acetals gave monotropolone (12) and bistropolone (13) derivatives at the benzylic position, whereas the related 1-ethoxyisochroman and the diethyl acetals of crotonaldehyde and cinnamaldehyde gave only the monotropolone derivatives (5, 10, or 11). The monotropolone derivatives (5, 10, 11, and 12) had poor potency against P388 leukemia in mice, but the bistropolone derivatives (13 and 14) showed significant potency and prolongation of life.