1. Cytotoxicity and Leishmanicidal Activity of Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemicarbazones
- Author
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Silvia Amaral Gonçalves Da-Silva, Josane A. Lessa, Raquel S. Amim, Marcus V. N. de Souza, Ana C. P. D. Rego, Gisele S. S. Firmino, Jackson A. L. C. Resende, Cláudia Pessoa, José Daniel Figueroa-Villar, and Adriane L. Nery
- Subjects
chemistry.chemical_classification ,isoniazid ,biology ,Stereochemistry ,Isoniazid ,Hydrazone ,Myeloid leukemia ,General Chemistry ,Leishmania ,biology.organism_classification ,Molecular biology ,thiosemicarbazone ,chemistry.chemical_compound ,hydrazone ,chemistry ,medicine ,cytotoxicity ,antileishmanial activity ,Cytotoxicity ,Amastigote ,Semicarbazone ,IC50 ,medicine.drug - Abstract
The isoniazid-derived hydrazones 2-pyridinecarbaldehyde- (HPCIH), 2-acetylpyridine- (HAPIH), 2-benzoylpyridine- (HBPIH), 2-pyridineformamide- (HPAmIH) and 2-pyrazineformamide- (HPzAmIH) isonicotinoyl hydrazones, as well as the pyrazinamide-derived thiosemicarbazones 2-pyrazineformamide- (HPzAm4DH), N(4)-methyl-2-pyrazineformamide- (HPzAm4M), N(4)-ethyl-2-pyrazineformamide- (HPzAm4E) and N(4)-phenyl-2-pyrazineformamide- (HPzAm4Ph) thiosemicarbazones, were assayed for their action against intracellular amastigote form of Leishmania (Viannia) braziliensis strains and the glioblastoma multiforme (SF-295), colon adenocarcinoma (HCT-116), ovarian cancer (OVCAR-8) and acute myeloid leukemia (HL-60) human tumor cell lines. All compounds exhibited leishmanicidal effects, with concentrations at which 50% of parasites were inhibited (IC50) in the 10.70-18.84 µM range. Moreover, the compounds were up to 30-fold less toxic to macrophages than to the parasites. Pyrazinamide-derived thiosemicarbazones proved to have poor activity against the tumor cell lines at 5 µg mL-1, whereas, in general the isoniazid-derived hydrazones presented good activity, being HAPIH and HBPIH the most potent compounds (IC50 = 0.42-1.5 µM).
- Published
- 2015