Chagas' disease is endemic in Latin America, affecting around 10 million people. Caused by the protozoan Trypanosoma cruzi, it is classified as a neglected tropical disease of high priority by the World Health Organization. The two available drugs were discovered in the 1970s and present several problems, including low efficacy and high toxicity. This scenario shows the urgent need for new therapeutic agents for the treatment of the disease. In this work, quantitative structure-activity relationships (QSAR) were investigated for a series of 88 pyridine derivatives bearing anti-T. cruzi activity. 3D QSAR models were generated employing the Comparative Molecular Similarity Indices Analysis (CoMSIA) approach. The generated CoMSIA models have high internal statistical consistency (r2 = 0.84 and q2 = 0.74), as well as predictive power for untested compounds (r2pred = 0.83), covering substantial structural diversity. The 3D isocontour surface maps indicated the essential structural features of the data set compounds related to biological activity. The results are valuable in suggesting interesting ways to the design and optimization of new structurally related analogs with improved potency.

3D QSAR studies for a series of antichagasic agents using comparative molecular similarity indices (CoMSIA)

248th National Meeting (2014)

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