Relationship between structure and antineoplastic activity of arylsulfonylhydrazones of 2-formylpyridine N-oxide

Abstract

The effects of various structural modifications on the antineoplastic activity of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide were ascertained in mice bearing either Sarcoma 180 or leukemia L1210. To accomplish this a variety of derivatives substituted at the aldehyde proton, the aryl ring, and the 4 position of the pyridine nucleus were synthesized. Antineoplastic activity was retained when nitro, amino, chloro, bromo, fluoro and methoxy groups were introduced into either the m or p positions of the phenyl ring of the parent compound. Substitution of the terminal phenyl group by a pyridine ring or by a bulky aromatic ring such as .alpha.-naphthyl, .beta.-naphthyl or fluorenyl did not abolish the marked antitumor activity expressed by this class of agents. Insertion of a nitro function or a morpholino group in the 4 position of the pyridine nucleus of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide resulted in 2 potent anticancer agents, while the introduction of a chloro function in the 4 position led to a pronounced decrease in biological activity. The essentiality of the aldehydic proton for tumor-inhibitory activity was demonstrated by the inactivity of 2 derivatives in which the aldehydic proton was replaced by a methyl group or by an oxygen atom.