Pd. Walzer et al., GUANYLHYDRAZONES IN THERAPY OF PNEUMOCYSTIS-CARINII PNEUMONIA IN IMMUNOSUPPRESSED RATS, Antimicrobial agents and chemotherapy, 38(11), 1994, pp. 2572-2576
Guanylhydrazones are cationic heteroaromatic drugs similar to the diam
idines 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
4'-formylphenyl)-1-methylimidazo-[1,2-a]pyridinium guanylhydrazones w
hich, at a dose of 2 mg/kg/day, were about as effective as trimethopri
m-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 w
ith oral administration. The 1,3-arylene diketone bis(guanylhydrazones
) were generally ineffective, although a triacetyl derivative showed s
ome anti-P. carinii activity. Nitroimidazole guanylhydrazone derivativ
es were also ineffective. Attempts to improve the therapeutic efficacy
of the different guanylhydrazones were limited by problems of toxicit
y. 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.