Loiseau P M
Université de Paris-Sud, Châtenay-Malabry, France.
Int J Parasitol. 1995 Mar;25(3):403-5. doi: 10.1016/0020-7519(94)00106-x.
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.
对作为DNA促旋酶抑制剂的4-氧代-1,4-二氢-3-吡啶羧酸的十种衍生物进行了体外和体内抗布氏布氏锥虫IPP的评估。两种化合物在孵育1小时后于100微摩尔浓度下具有体外活性。孵育24小时后，有8种化合物具有活性，最有趣的化合物1-(4-羟基-2-甲基苯基)-6-[2-(4,5-二氯苯基)-乙烯基]-4-氧代-1,4-二氢吡啶-3-羧酸（化合物8号）在10微摩尔浓度下具有杀锥虫活性。皮下单次给药50微摩尔/千克后，在体内未观察到杀锥虫作用。体外杀锥虫作用与DNA促旋酶抑制相关。
