Target-based Screening of the Chagas Box: Setting Up Enzymatic Assays to Discover Specific Inhibitors Across Bioactive Compounds

Author(s): Emir Salas-Sarduy, Gabriela T. Niemirowicz, Juan José Cazzulo, Vanina E. Alvarez*

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 36 , 2019


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Abstract:

Chagas disease is a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. The disease is endemic in Latin America with about 6 million people infected and many more being at risk. Only two drugs are available for treatment, Nifurtimox and Benznidazole, but they have a number of side effects and are not effective in all cases. This makes urgently necessary the development of new drugs, more efficient, less toxic and affordable to the poor people, who are most of the infected population. In this review we will summarize the current strategies used for drug discovery considering drug repositioning, phenotyping screenings and target-based approaches. In addition, we will describe in detail the considerations for setting up robust enzymatic assays aimed at identifying and validating small molecule inhibitors in high throughput screenings.

Keywords: Chagas disease, tropical illness, protozoan parasite, Trypanosoma cruzi, Nifurtimox and Benznidazole, drug repositioning, phenotyping screenings.

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