Antineoplastic and biochemical properties of arylsulfonylhydrazones of 2 formylpyridine N oxide

Article abstract of DOI:10.1021/jm00228a019

The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2 formylpyridine N oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene quinoline, or isoquinoline resulted in loss of activity, (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N oxide produced inactive agents, (c) the pyridine N oxide function was essential for anticancer activity, except for 4 substituted derivatives which were active without the N oxide group, (d) replacement of the SO₂ group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO₂ and aryl ring with retention of anticancer potency. One of the most active members of this series, 1 oxidopyridine 2 carboxaldehyde p toluenesulfonylhydrazone exhibited antineoplastic, activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to α (N) heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine ³H and uridine ³H incorporation into DNA and RNA respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound.