Hydroxy-2-formylpyridine thiosemicarbazones

The hydroxylated derivatives, 5-hydroxy-2-formylpyridine thiosemicarbazone and 3-hydroxy-2-formylpyridine thiosemicarbazone, show a different pattern of inhibition [74]. They appear competitive with iron and either non-competitive or uncompetitive with the dithiol substrate the imprecise nature of the assay does not allow a choice between these alternatives. The failure of the dithiol to reverse inhibition of ribonucleoside diphosphate reductase by the hydroxylated derivatives implies that the interaction of these inhibitors with the enzyme occurs at a site different from that involved in the action of (4) and (1). The impure nature of this complex enzyme system, however, makes it impossible to explain fully these differences and further advances will require the availability of a highly purified enzyme. 

Hydroxy-2-formylpyridine thiosemicarbazone is the only member of this series that has been administered to man as part of a Phase I study [55,56]. The selec-... 

C7H8N2S, 2-Methyl-4-thiocarbamoylpyridine, 34B, 130, 136 C7H8Ni,OS 1.5 H2O, 5-Hydroxy-2-formylpyridine thiosemicarbazone sesquihydrate, 40B, 67... 

Methisazone inactivates a wide spectrum of tumour-causing viruses (RNA types) is tissue-culture (Levinson, Woodson, and Jackson, 1971). A simpler analogue, 5-hydroxy-2-formylpyridine thiosemicarbazone, was found to be highly active against several types of experimental cancer in mice, when given intraperitoneally (Blanz and French, 1968). 

A series of meta and para substituted 3- and 5-benzyloxy derivatives of 2-formylpyridine thiosemicarbazone has been synthesized both to explore and to utilize a hypothetical hydrophobic binding zone adjacent to the major inhibitor binding site of the target enzyme, ribonucleoside diphosphate reductase [20]. These agents were synthesized by condensing a nitrobenzyl bromide (19) with 3-or 5-hydroxy-2-hydroxymethylpyridine (18), followed by oxidation with MnOj... 

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