Synthesis, 2D-QSAR Studies and Biological Evaluation of Quinazoline Derivatives as Potent Anti-Trypanosoma cruzi Agents

摘要

Background: Chagas disease affects about 7 million people worldwide. Only two drugsare currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) andnifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease.Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives.Objective: The development of safer and more efficient therapeutic anti-T. cruzi drugs continues tobe a major goal in trypanocidal chemotherapy.Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinoneand quinazoline derivatives were studied as trypanocidal agents. All compounds were screened invitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes.Results: Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and13p) displayed significant activity against both epimastigotes and tripomastigotes, without exertingtoxicity on Vero cells.Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives representsan interesting starting point for a medicinal chemistry program aiming at the development ofnovel chemotherapies for Chagas disease.