title: Synthesis and antileishmanial evaluation of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazole derivatives.
abstract: A series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a-g) and 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a-g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC(50) values ranging from 15 to 60 μM. The reference drug pentamidine presented IC(50)=10 μM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control.
authors: Departamento de Física e Química, Instituto de Ciências Exatas, Universidade Federal de Itajubá, 37500-903 Itajubá, MG, Brazil. mauriciounifei@yahoo.com.br
authors: Maurício S
authors: MS
authors: dos Santos
authors: Mariana L V
authors: ML
authors: Oliveira
authors: Alice M R
authors: AM
authors: Bernardino
authors: Rosa M
authors: RM
authors: de Léo
authors: Veronica F
authors: VF
authors: Amaral
authors: Flavia T
authors: FT
authors: de Carvalho
authors: Leonor L
authors: LL
authors: Leon
authors: Marilene M
authors: MM
authors: Canto-Cavalheiro
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007891:Leishmania / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D007093:Imidazoles; D011720:Pyrazoles; C031280:pyrazole; C029899:imidazole