Cytotoxicity and leishmanicidal activity of isoniazid-derived hydrazones and 2-pyrazineformamide thiosemicarbazones

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. Pyrazinamidederived 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).