Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6310-2. doi: 10.1016/j.bmcl.2013.09.062.

Jéssica V Faria ¹, Maurício S dos Santos, Alice M R Bernardino, Klaus M Becker, Gérzia M C Machado, Raquel F Rodrigues, Marilene M Canto-Cavalheiro, Leonor L Leon

Affiliations

Affiliation

1 Departamento de Química Orgânica, Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil.

PMID: 24125880 DOI: 10.1016/j.bmcl.2013.09.062

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.

Keywords

Antileishmanial activity; Leishmania amazonensis; Leishmania braziliensis; Tetrazole.

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