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Medicinal Chemistry

Author(s): Mariela Bollini, Ana M. Bruno*, María E. Niño, Juan J. Casal, Leandro D. Sasiambarrena, Damián A.G. Valdez, Leandro Battini, Vanesa R. Puente and María E. Lombardo

DOI: 10.2174/1573406414666181005145042

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

Page: [265 - 276] Pages: 12

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Abstract

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.

Keywords: Chagas disease, quinazoline derivatives, QSAR, trypanosoma cruzi, physicochemical properties, drug discovery.

Graphical Abstract

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