Parasitic infections continue to be societal and health burdens, affecting millions of people, mainly in developing countries. The high toxicity, lack of efficacy, resistance, and high cost, highlight the need for the development of new antiparasitic drugs. Here, we present the analysis of the structural and physicochemical properties of compounds tested against T. cruzi reported in the ChEMBL database. 3-benzoylisoquinolones were synthesized via Gabriel-Colman rearrangement, and subsequent electrophilic aromatic substitution at position 3 of the benzoyl ring. Two of the samples evaluated exhibited greater trypanocidal activity than the reference drug benznidazole at the assayed concentrations. Chemical space projection of the synthesized compounds along with 3067 structures with known activities against T. cruzi shows that the isoquinolones occupy a sparsely-populated region of chemical space. In addition, 2D and 3D structural similarity analyses revealed micromolar and submicromolar inhibitors of T. cruzi in ChEMBL with high similarity to the synthesized molecules.

Structural and physicochemical properties of anti-Chagas agents reported in the ChEMBL database and identification of benzoylisoquinolines as potential trypanocidal agents

244th National Meeting (2012)

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