Action of DNA-gyrase inhibiting derivatives of 4-oxo-1, 4-dihydro-3-pyridinecarboxylic acid against Trypanosoma brucei.
Ten derivatives of 4-oxo-1,4-dihydro-3-pyridinecarboxylic acid as DNA-gyrase inhibitors were evaluated in vitro and in vivo against Trypanosoma brucei brucei IPP. Two compounds were were active at 100 microM in vitro after 1 h incubation time. After 24 h incubation, 8 compounds were active and the most interesting compound, 1-(4-hydroxy-2-methyl-phenyl)-6-[2-(4,5-dichloro-phenyl)-ethenyl] -4-oxo-1, 4-dihydropyridine-3-carboxylic acid (compound No. 8) was trypanocidal at 10 microM. The trypanocidal effects were not noted in vivo after subcutaneous treatment administered as a single dose of 50 mumols/kg. The in vitro trypanocidal effect is correlated with the DNA-gyrase inhibition.
Loiseau
P M
PM
Université de Paris-Sud, Châtenay-Malabry, France.
D000818:Animals; D004341:Drug Evaluation; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000472:pathogenicity; D014774:Virulence / Q000187:drug effects
D009539:Nicotinic Acids; D059005:Topoisomerase II Inhibitors; D014344:Trypanocidal Agents; C094459:4-oxo-1,4-dihydro-3-pyridinecarboxylic acid