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.

Keywords: 3-Benzoylpyridazine 2′-pyridylhydrazones; Antitumor activity; Colony forming assay; Cytotoxic activity.