Thiosemicarbazones, anticancer

Bis(thiosemicarbazones) [89-97] and AT-heterocyclic thiosemicarbazones comprise two interesting series of experimental chemotherapeutic agents. 2-formylpyridine thiosemicarbazone, the first of the latter series to be examined for biological activity, showed mild antileukemic activity against 1-1210 tumor in mice [98]. However, it was found to be toxic at the therapeutic dose levels which led to synthesis of other aromatic and heterocyclic thiosemicarbazones as potential agents [80, 99, 100]. However, the only active anticancer compounds besides glyoxal bis(thiosemicarbazones) were the iV-heterocyclic thiosemicarbazones [101], 2 formyl-3-hydroxypyridine thiosemicarbazone [102] and... 

Krishna G, Mao J, Almassian B. Development of a parenteral formulation of an investigational anticancer drug, 3-aminopyr-idine-2-carboxaldehyde thiosemicarbazone. Pharm Dev Technol 1999 4 71-80. 

Patole, J. Padhye, S. Padhye, S. Newton, C. J. Anson, C. Powell, A. K. Synthesis, characterization and in vitro anticancer activities of semicarbazone and thiosemicarbazone derivatives of salicylaldehyde and their copper complexes against human breast cancer cell line MCF-7. Indian J. Chem., Sect. A 2004, 43A, 1654-1658. 

French and Blanz [9-13] extended these observations by testing a series of formyl heteroaromatic thiosemicarbazones for anticancer activity several of these derivatives, especially 1-formylisoquinoline thiosemicarbazone [10], 2-formyl-3-hydroxypyridine thiosemicarbazone [11] and 2-formyl-5-hydroxy-pyridine thiosemicarbazone [13] showed significant tumour-inhibitory activity when tested against a spectrum of transplanted murine neoplasms. 

Anticancer examples, Thiosemicarbazones have been mentioned above in connexion with their antiviral and antitubercular properties. They also have anticancer activity, as already mentioned for 5-hydroxypicolinic aldehyde thiosemicarbazone (4.18) in Section 4.0. Such substances powerfully inhibit ribonucleoside diphosphate reductase, the enzyme which converts ribo- to deoxyribo- nucleotides, leading to inhibition of DNA synthesis. Interaction with the enzymatically-required iron by these drugs in thought to lie at the root of their action (Agrawal, et al,y 1972). 

---