3 research outputs found
1‑Benzyl-3-aryl-2-thiohydantoin Derivatives as New Anti-<i>Trypanosoma brucei</i> Agents: SAR and in Vivo Efficacy
No full textA high
throughput screening and subsequent hit validation identified
compound <b>1</b> as an inhibitor of <i>Trypanosoma brucei</i> parasite growth. Extensive structure–activity relationship
optimization based on antiparasitic activity led to the highly potent
compounds, 1-(4-fluorobenzyl)-3-(4-dimethylamino-3-chlorophenyl)-2-thiohydantoin
(<b>68</b>) and 1-(2-chloro-4-fluorobenzyl)-3-(4-dimethylamino-3-methoxyphenyl)-2-thiohydantoin
(<b>76</b>), with a <i>T. brucei</i> EC<sub>50</sub> of 3 and 2 nM, respectively. This represents >100-fold improvement
in potency compared to compound <b>1</b>. In vivo efficacy experiments
of <b>68</b> and <b>76</b> in an acute mouse model of
Human African Trypanosomiasis showed a 100% cure rate after 4 days
of oral treatment at 50 mg/kg twice per day
