Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp
| Autor: | Maurício S. dos Santos, Alice M. R. Bernardino, Klaus M. Becker, Marilene M. Canto-Cavalheiro, Leonor L. Leon, Gerzia M. C. Machado, Jéssica V. Faria, Raquel Fonseca Rodrigues |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Antiprotozoal Agents Tetrazoles Pharmaceutical Science Pyrazole Biochemistry Cell Line Mice Structure-Activity Relationship chemistry.chemical_compound Nitriles Drug Discovery medicine Animals Tetrazole Cytotoxicity Molecular Biology IC50 Leishmania Dose-Response Relationship Drug biology Chemistry Organic Chemistry Stereoisomerism biology.organism_classification Leishmania braziliensis In vitro Immunology Pyrazoles Molecular Medicine Pentamidine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 23:6310-6312 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect