title: Synthesis and leishmanicidal activities of 1-(4-X-phenyl)-N'-[(4-Y-phenyl)methylene]-1H-pyrazole-4-carbohydrazides.
abstract: 1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal in vitro activities and cytotoxic effects were investigated. The drugs prototypes of these new compounds (ketoconazole, benznidazole, allopurinol and pentamidine) were also tested. It was found that among all the 1H-pyrazole-4-carbohydrazides derivatives examined, the most active compounds were those with X = Br, Y = NO2 (27) and X = NO2, Y = Cl (15) derivatives which showed to be most effective on promastigotes forms of L. amazonensis than on L. chagasi and L. braziliensis species. When tested against murine peritoneal macrophages as mammalian host cell controls of toxicity, 1-(4-Br-phenyl)-N'-[(4-NO(2)-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (27) (EC50 = 50 microM l(-1)) and 1-(4-NO2-phenyl)-N'-[(4-Cl-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) EC50 = 80 microM l(-1))] was reasonably toxic. However, both compounds were less toxic than pentamidine and ketoconazole. These results provide new perspectives on the development of drugs with activities against Leishmania parasite.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Programa de Pós-graduação em Química Orgânica, Universidade Federal Fluminense, Outeiro de São João Baptista, CEP 24020-150, Niterói, RJ, Brazil. alice@rmn.uff.br
authors.forename: Alice M R
authors.initials: AM
authors.lastname: Bernardino
authors.forename: Adriana O
authors.initials: AO
authors.lastname: Gomes
authors.forename: Karen S
authors.initials: KS
authors.lastname: Charret
authors.forename: Antônio C C
authors.initials: AC
authors.lastname: Freitas
authors.forename: Gérzia M C
authors.initials: GM
authors.lastname: Machado
authors.forename: Marilene M
authors.initials: MM
authors.lastname: Canto-Cavalheiro
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
authors.forename: Veronica F
authors.initials: VF
authors.lastname: Amaral
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D007896:Leishmaniasis / Q000188:drug therapy; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D006834:Hydrazines; D011720:Pyrazoles; C031280:pyrazole; C019289:carbohydrazide