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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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Faria JV,dos Santos MS,Bernardino AM,Becker KM,Machado GM,Rodrigues RF,Canto-Cavalheiro MM,Leon LL

doi

10.1016/j.bmcl.2013.09.062

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

6310-2

issue

23

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)01136-0

journal_volume

23

pub_type

杂志文章

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