Effect of oral treatment with pyrazole carbohydrazide derivatives against murine infection by Leishmania amazonensis.
Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO(2) and X = NO(2)/Y = Cl were independently investigated in the CBA mouse model of cutaneous leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohydrazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspartate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against leishmaniasis.
Charret
Karen S
KS
Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Rodrigues
Raquel F
RF
Bernardino
Alice M R
AM
Gomes
Adriana O
AO
Carvalho
Adriana V
AV
Canto-Cavalheiro
Marilene M
MM
Leon
Leonor
L
Amaral
Veronica F
VF
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007894:Leishmania mexicana / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D008198:Lymph Nodes / Q000469:parasitology; D008214:Lymphocytes; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015394:Molecular Structure; D009504:Neutrophils; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
D000981:Antiprotozoal Agents; D006834:Hydrazines; D011720:Pyrazoles; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C019289:carbohydrazide