TRYPANOCIDAL ACTIVITY OF SYNTHETIC HETEROCYCLIC-DERIVATIVES OF ACTIVEQUINONES FROM TABEBUIA SP

Continuing a program-on the chemistry and biological activity of compo unds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoi midazole derivatives obtained from the reaction of naphtoquinones isol ated from Tabebuia sn (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl der ivatives of lawsone, a natural quinone from Lausonia alba inactive aga inst T cruzi, is reported. The introduction of an allyl group in lawso ne gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activ ity against the parasite: with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mu mol/l, respectively. The trypanocidal activity of the nap htho heterocyclics synthesized from the original quinones showed no co ncordant behavior in relation to the parent compound. Sir; of nine of the synthesized compounds presented lower ID50 values than crystal vio let, indicating a general trend of activity among naphthalenic heteroc yclics of the oxazole/imidazole type. However. their chemical structur es do not endow them with the capacity of free radical generation by b iological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazo le, responsible for such behaviour. As a hypothesis, the pattern of th eir biological actions should be focused in other aspects of their che mical structures. Because of their polycyclic planar topology, these d erivatives are potential candidates for experimental tests as DNA inte rcalating agents.