Publications by authors named "E De Hostos"

In efforts towards eliminating malaria, a discovery program was initiated to identify a novel antimalarial using KAF156 as a starting point. Following the most recent TCP/TPP guidelines, we have identified mCMQ069 with a predicted single oral dose for treatment (∼40-106 mg) and one-month chemoprevention (∼96-216 mg). We have improved unbound MPC and predicted human clearance by 18-fold and 10-fold respectively when compared to KAF156.

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Cholera remains a major cause of infectious diarrhea globally. Despite the increased availability of cholera vaccines, there is still an urgent need for other effective interventions to reduce morbidity and mortality. Furthermore, increased prevalence of antibiotic-resistant Vibrio cholerae threatens the use of many drugs commonly used to treat cholera.

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Background: Soil-transmitted helminths (STHs) are parasitic nematodes that inhabit the human intestine. They affect more than 1.5 billion people worldwide, causing physical and cognitive impairment in children.

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The intestinal protozoan is a leading cause of diarrheal disease and mortality in young children. There is currently no fully effective treatment for cryptosporidiosis, which has stimulated interest in anticryptosporidial development over the last ∼10 years, with numerous lead compounds identified, including several tRNA synthetase inhibitors. Here, we report the results of a dairy calf efficacy trial of the methionyl-tRNA ( MetRS [MetRS]) synthetase inhibitor 2093 and the spontaneous emergence of drug resistance.

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Article Synopsis
  • Researchers developed two groups of new inhibitors for the enzyme methionyl-tRNA synthetase (MetRS) found in parasites, utilizing different chemical linkers in their design.
  • Both groups of inhibitors were effective at low concentrations (EC < 10 nM) in stopping parasite growth, while showing minimal toxicity to human cells (CCs > 20,000 nM).
  • Despite their effectiveness, the inhibitors had limited ability to cross the blood-brain barrier, indicating that further modifications are needed for treatment in advanced cases of human African trypanosomiasis.
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