title: Synthesis, cytotoxic, and antitumor activities of 2-pyridylhydrazones derived from 3-benzoylpyridazines.
abstract: A series of 2-pyridylhydrazones derived from phenyl-pyridazin-3-yl-methanones were prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Whereas hydrazones derived from 3-benzoylpyridazines (IC50  = 0.99-8.74 µM) inhibited the proliferation of the tumor cell lines tested, the non-fully aromatic 3-benzoylpyridazinone hydrazones (IC50  >10 µM) turned out to be inactive. Compounds E-1b (IC50  = 0.12 µM) and E-1d (IC50  = 0.18 µM) exert high cytotoxic activities in clonogenic assays involving human tumor cells of different tissue origins. In vivo application of compound E-1b (300 mg/kg/day) resulted in a 66% reduction in tumor burden.
authors.affiliation: Pharmaceutical Chemistry-Institute of Pharmacy, Centrum für Chemie und Biomedizin, Leopold-Franzens-Universität, Innsbruck, Austria.
authors.forename: Johnny
authors.initials: J
authors.lastname: Easmon
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pürstinger
authors.forename: Gottfried
authors.initials: G
authors.lastname: Heinisch
authors.forename: Hans H
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Johann
authors.initials: J
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008819:Mice, Nude; D015394:Molecular Structure; D009928:Organ Specificity; D011724:Pyridazines / Q000737:chemistry*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D011724:Pyridazines
keywords: 3-Benzoylpyridazine 2′-pyridylhydrazones; Antitumor activity; Colony forming assay; Cytotoxic activity