Baillet S, Buisine E, Horvath D, Maes L, Bonnet B, Sergheraert C
Institut Pasteur de Lille, URA 1309 CNRS, Faculté de Pharmacie, France.
Bioorg Med Chem. 1996 Jun;4(6):891-9. doi: 10.1016/0968-0896(96)00083-1.
A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within the synthesized series confirmed the main working hypothesis inspired by the molecular modeling study. The different compounds were tested in vitro on the enzyme and on Trypanosoma cruzi and Trypanosoma brucei trypomastigotes as well as in vivo in infected mice.
一项旨在检测锥虫硫醇还原酶（TR）活性位点中类药效团模式的分子建模研究，为合成和测试具有延长或分支多氨基侧链的二苯硫醚衍生物作为潜在TR抑制剂的可能性提供了线索。合成系列中的抑制结果证实了分子建模研究所激发的主要工作假设。对不同的化合物进行了体外酶活性测试、对克氏锥虫和布氏锥虫锥鞭毛体的测试以及在感染小鼠体内的测试。
