title: Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp.
abstract: A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24h=15±0.14 μM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24h=26±0.09 μM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC50=13±0.04 μM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L.braziliensis than on L. amazonensis.
authors.affiliation: Departamento de Química Orgânica, Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil.
authors.forename: Jéssica V
authors.initials: JV
authors.lastname: Faria
authors.forename: Maurício S
authors.initials: MS
authors.lastname: dos Santos
authors.forename: Alice M R
authors.initials: AM
authors.lastname: Bernardino
authors.forename: Klaus M
authors.initials: KM
authors.lastname: Becker
authors.forename: Gérzia M C
authors.initials: GM
authors.lastname: Machado
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Rodrigues
authors.forename: Marilene M
authors.initials: MM
authors.lastname: Canto-Cavalheiro
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007891:Leishmania / Q000187:drug effects*; D051379:Mice; D009570:Nitriles / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D009570:Nitriles; D011720:Pyrazoles; D013777:Tetrazoles; C045574:1H-tetrazole
keywords: Antileishmanial activity; Leishmania amazonensis; Leishmania braziliensis; Tetrazole