title: 2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells.
abstract: 2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO(2)Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO(2)Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC(50) values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI = IC(50MRC5)/IC(50glioma)) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors.
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Angel A R
authors.initials: AA
authors.lastname: Despaigne
authors.forename: Gabrieli L
authors.initials: GL
authors.lastname: Parrilha
authors.forename: Jans B
authors.initials: JB
authors.lastname: Izidoro
authors.forename: Pryscila R
authors.initials: PR
authors.lastname: da Costa
authors.forename: Raquel G
authors.initials: RG
authors.lastname: dos Santos
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Piro
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castellano
authors.forename: Willian R
authors.initials: WR
authors.lastname: Rocha
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005708:Gallium / Q000737:chemistry*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D011725:Pyridines; C543930:2-acetylpyridine; D005708:Gallium