Van Landingham R M, Walker L L, O'Sullivan J F, Shinnick T M
Division of Bacterial and Mycotic Diseases, Centers for Disease Control, Atlanta, Georgia 30333.
Int J Lepr Other Mycobact Dis. 1993 Sep;61(3):406-14.
Twenty-five compounds structurally related to clofazimine were tested for their ability to inhibit the growth of Mycobacterium leprae using the kinetic method of drug evaluation in the mouse foot pad model of leprosy. Seven of the phenazine derivatives displayed anti-M. leprae activity comparable to that of clofazimine when administered at a concentration of 0.01% (w/w) in the diet. Three of the compounds, B746, B4087, and B4101, were active when administered at 0.001% in the diet. At a dietary concentration of 0.0001%, B4087 and B4101 were slightly more active than clofazimine, while B746 was less active. In the kinetic method of drug evaluation, greater anti-M. leprae activity of phenazine derivatives was generally associated with greater pigmentation of abdominal fat. Of the compounds which did not cause pigmentation when fed at a concentration of 0.01% in the diet B4090 was the most active. This compound also inhibits the growth of a clofazimine-resistant M. smegmatis strain.
利用麻风病小鼠足垫模型中的药物动力学评估方法，对25种与氯法齐明结构相关的化合物进行了测试，以考察它们抑制麻风分枝杆菌生长的能力。当以0.01%（w/w）的浓度添加到饲料中时，7种吩嗪衍生物显示出与氯法齐明相当的抗麻风分枝杆菌活性。其中3种化合物，即B746、B4087和B4101，当以0.001%的浓度添加到饲料中时具有活性。在饲料浓度为0.0001%时，B4087和B4101的活性略高于氯法齐明，而B746的活性较低。在药物动力学评估方法中，吩嗪衍生物较强的抗麻风分枝杆菌活性通常与腹部脂肪色素沉着增加有关。在饲料中添加浓度为0.01%时不引起色素沉着的化合物中，B4090活性最高。该化合物还能抑制对氯法齐明耐药的耻垢分枝杆菌菌株的生长。
