RESUMO
Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents.
Assuntos
Compostos Heterocíclicos/síntese química , Plantas Medicinais/química , Quinonas/síntese química , Tripanossomicidas/síntese química , Animais , Brasil , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Compostos Heterocíclicos/farmacologia , Substâncias Intercalantes/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Naftoquinonas/síntese química , Naftoquinonas/farmacologia , Quinonas/isolamento & purificação , Quinonas/farmacologia , Espectrofotometria Infravermelho , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Several synthetic, semi-synthetic and natural compounds as well as plant extracts were screened for their growth inhibition activity on KB cells. The most active ones were naphthoquinones and derivatives of pyrido [4,3-b]carbazole alkaloids, with inhibition dose (ID50) less than 4 micrograms/ml. Of the crude extracts of several plants screened, Vellozia caput-ardeae showed to be the most active.