Synthesis, cytotoxic, and antitumor activities of 2-pyridylhydrazones derived from 3-benzoylpyridazines.
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.
['Easmon|Johnny|J|', 'Pürstinger|Gerhard|G|', 'Heinisch|Gottfried|G|', 'Fiebig|Hans H|HH|', 'Roth|Thomas|T|', 'Hofmann|Johann|J|']
D000818:Animals D000970:Antineoplastic Agents D049109:Cell Proliferation D002470:Cell Survival D004305:Dose-Response Relationship, Drug D006801:Humans D006835:Hydrazones D020128:Inhibitory Concentration 50 D008819:Mice, Nude D015394:Molecular Structure D009928:Organ Specificity D011724:Pyridazines D014410:Tumor Stem Cell Assay D023041:Xenograft Model Antitumor Assays
Antitumor activity Cytotoxic activity 3-Benzoylpyridazine 2′-pyridylhydrazones Colony forming assay