The present work describes the synthesis of 22 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and 12 compounds exhibited an in vitro EC ≤ 1 μM against () and () parasites, respectively. Based on promising results of activity (EC < 100 nM), cytotoxicity, metabolic stability, protein binding, and pharmacokinetics (PK) properties, compound was selected as a candidate for efficacy studies. This compound was screened in an acute mouse model against ( strain). After established infection, mice were dosed twice a day for 5 days, and then monitored for 6 weeks using an imaging system (IVIS). Compound demonstrated parasite inhibition comparable to the benznidazole treatment group. Compound represents a potential lead for the development of drugs to treat trypanosomiasis.
The Front Cover shows efforts among Brazilian, American, and European researchers to combat neglected tropical diseases. New heterocyclic compounds based on imidazopyridine/pyrimidine and furopyridine cores originating from Brazil travel to the USA and Europe to be developed as anti‐infective agents against Trypanosomiases. By exploring the chemical diversity at eight different positions of the central core, we obtained various heterocyclic compounds having significant potential for anti‐trypanosomiases drug discovery. More information can be found in the Full Paper by Daniel G. Silva, Flavio S. Emery et al. Cover design by Daniel Gedder Silva.
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