Heterocyclic carboxaldehyde

The Chemistry and Biological Activity of a -(AO-Heterocyclic Carboxaldehyde Thiosemicarbazones... 

The synthesis of iron, cobalt and nickel complexes of 2-formylpyridine thiosemicarbazone has been reported [59]. The a-(AO-heterocyclic carboxaldehyde thlosemicarbazones strongly complex transition metals through their N -N -S ... 

The geometrical isomers of the thiosemicarbazones of 2-formylpyridine (4) and 1-foimylisoquinoline (1) have been synthesized and their structures studied by spectroscopic methods [69]. X-Ray diffraction studies of bis(isoquinoline-l-carboxaldehyde thiosemicarbazanato)nickel(ll) monohydrate by Mathew and Palenik [49] have demonstrated that the transition metal binds with the thiol form (118) of the a-(AO-heterocyclic carboxaldehyde thiosemicarbazones. The... 

The a-(AO-heterocyclic carboxaldehyde thiosemicarbazones are primarily inhibitors of the synthesis of DNA in neoplastic cells [57,70] therefore, they exert their effect in the S phase of the cell cycle [71,72]. Inhibition of the biosynthesis of RNA and protein is also produced by agents of this class however, these metabolic processes are considerably less sensitive than is the replication of DNA [57,70,73-75]. Interference with the biosynthesis of DNA by these agents was shown to be due to inhibition of the enzyme ribonucleoside diphosphate reductase [70,73,74,76]. The a-(AO-heterocyclic carboxaldehyde thiosemicarbazones constitute, as a class, the most potent known inhibitors of ribonucleoside diphosphate reductase, being 80-5000 times more effective than the classical inhibitor of this enzyme, hydroxyurea [for appropriate references see 77]. 

The kinetic mechanism of inhibition of ribonucleoside diphosphate reductase by a-(AO-heterocyclic carboxaldehyde thiosemicarbazones is not clear. The concentrations of the nucleoside diphosphate substrate, the allosteric activator ATP, or magnesium ion do not influence the inhibition of the enzyme produced by all of the thiosemicarbazones tested to date. Interesting differences exist, however, between the ring hydroxylated and nonhydroxylated a-(AO-heterocyclic carbox-... 

The primary lesion created in cells by the heterocyclic carboxaldehyde thiosemicarbazones is interference with the biosynthesis of DNA, and this action is primarily due to the potent inhibition of ri-bonucleoside diphosphate reductase activity. 5-Hydroxypicolinaldehyde thiosemicarbazone (NSC-107392) inhibits ribonucleoside diphosphate reductase by the chelation of iron. Krakoff et al. (1974) tried the drug by intravenous injection to 30 patients with leukaemia or various solid tumours. Marked haemolysis, iron chelation, and urinary excretion of iron occurred. 

The Passerini reaction has also been utilized as a method for the homologation of heterocyclic carboxaldehydes. Studies by Weinreb and coworkers, directed toward the synthesis of amphimedine, have used a Passerini reaction for the homologation of the methoxypyridine derivative 65 with methyl isocyanide and acetic acid in methanol to give 66 in 77% yield. 

The a-(AO-heterocyclic carboxaldehyde thiosemicarbazones constitute a class of agents which possess both antineoplastic and antiviral activity [1]. The first agent of this series to be examined for biological activity, 2-formylpyridine thio-... 

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