Cytotoxicity and Leishmanicidal Activity of Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemicarbazones

• Published in: Journal of the Brazilian Chemical Society 2016-04, Vol.27 (4), p.769-777
• Main Authors: Amim, Raquel S., Firmino, Gisele S. S., Rego, Ana C. P. D., Nery, Adriane L., Da-Silva, Silvia A. G., Souza, Marcus V. N. de, Pessoa, Claudia, Resende, Jackson A. L. C., Figueroa-Villar, José D., Lessa, Josane A.
• Format: Article
• Language: English
• Subjects: CHEMISTRY, MULTIDISCIPLINARY
• ISSN: 0103-5053; 1678-4790
• DOI: 10.5935/0103-5053.20150330

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).