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

Journal of the Brazilian Chemical Society

Da-Silva, Silvia A. G.¹  Lessa, Josane A.¹  Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil¹  Rego, Ana C. P. D.¹  Figueroa-Villar, José D.¹  Resende, Jackson A. L. C.¹  Fundação Oswaldo Cruz, Rio de Janeiro, Brazil¹  Souza, Marcus V. N. de¹  Instituto Militar de Engenharia, Rio de Janeiro, Brazil¹  Amim, Raquel S.¹  Universidade Federal do Ceará, Fortaleza, Brazil¹  Universidade Federal Fluminense, Niterói, Brazil¹  Nery, Adriane L.¹  Firmino, Gisele S. S.¹  Pessoa, Claudia¹ 

关键词:  antileishmanial activity;    cytotoxicity;    isoniazid;    hydrazone;    thiosemicarbazone;   

DOI  :  10.5935/0103-5053.20150330

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

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).

【 授权许可】

Unknown