Background:
Chagas disease affects about 7 million people worldwide. Only two drugs
are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and
nifurtimox (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 to
be a major goal in trypanocidal chemotherapy.
Method:
Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone
and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in
vitro 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 and
13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting
toxicity on Vero cells.
Conclusion:
The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents
an interesting starting point for a medicinal chemistry program aiming at the development of
novel chemotherapies for Chagas disease.
Investigation of some benzoquinazoline and quinazoline derivatives as novel inhibitors of HCV-NS3/4A protease: biological, molecular docking and QSAR studies