Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.
Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.
复制标题
脒基腙治疗免疫抑制大鼠卡氏肺孢子虫肺炎。
DOI：
10.1128/aac.38.11.2572
复制
发表时间：
1994
影响因子：
4.9
通讯作者：
Sundberg,RJ
中科院分区：
文献类型：
--
作者：
Walzer,PD;Foy,J;Runck,J;Steele,P;White,M;Klein,RS;Otter,BA;Sundberg,RJ
Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.
