Diseño, síntesis y evaluación biológica de nuevos derivados de 1,4-di-n-óxido de quinoxalina como agentes antimaláricos y leishmanicidas

Abstract

Malaria is by far the world¿s most important tropical parasitic disease and one of the oldest diseases known to mankind. Leishmaniasis is generally recognized for its cutaneous form which causes non-fatal disfiguring lesions, although epidemics of the potentially fatal visceral form cause thousands of deaths. The emergence of resistant parasites, the high cost and toxicity of current treatments call for the discovery of new drugs. The quinoxaline derivatives show very interesting biological properties and their interest in Medicinal Chemistry is still in progress. The oxidation of both nitrogens of this heterocyclic system in order to obtain quinoxaline 1,4-di-N-oxide derivatives increases the biological properties enormously. The experimental work presented in this memory is based on the fusion between quinoxaline 1,4-di-N-oxide derivatives and some active compounds against malaria and leishmania. This design is focused on the molecular hybridization as a strategy of combination of pharmacophoric moieties of different bioactive substances for producing a new hybrid compound with improved affinity and efficacy. As a result of different research projects, forty eight compounds have been designed, synthesized and evaluated in vitro against Plasmodium falciparum, Leishmania amazonensis and Leishmania infantum. The toxicity was also evaluated. Four compounds are highly active against Plasmodium falciparum, other four compounds are highly active against Leishmania amazonensis and seven against Leishmania infantum. Two compounds present better selectivity index than Amphotericin B.