Iron anticancer activity

Other metal complexes also have promising anticancer activity. Two Ti(IV) complexes are on clinical trial, an acetylacetonate derivative (budotitane) and titanocene dichloride, and the antimetastic activity of octahedral Ru(III) complexes is attracting attention, one of which is now on clinical trial. Ru(III), like several other metal ions, can be delivered to cells via the iron transport protein transferrin. 

Anthracydines have several modes of action leading to anticancer activity. They intercalate between base pairs in DNA, interfering with nucleic acid synthesis. Anthracydines also inhibit DNA topoisomerases I and II, which leads to DNA double-strand breaks. In addition, doxorubicin and daunorubicin may form complexes with metals such as iron. Although these metal-anthracycline complexes result in oxygen free radical formation, which may contribute to antitumor activity, membrane damage incurred from the free radicals is thought to be the mechanism responsible for... 

Iron bleomycin (FeBLM) is a natural product with anticancer activity that is thought to arise from nucleic acid damage and has been termed... 

These water-soluble PFS derivatives are of potential interest as electrode materials and as redox-active polymeric electrolytes for which the ionic conductivity might be tuned by oxidation of the iron centers. These materials may also prove usefid as exploratory redox-controUed drug delivery agents as various water-soluble ferrocenimn salts have been shown to display anticancer activity. 

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). 

There are various pathways for free radical-mediated processes in microsomes. Microsomes can stimulate free radical oxidation of various substrates through the formation of superoxide and hydroxyl radicals (the latter in the presence of iron) or by the direct interaction of chain electron carriers with these compounds. One-electron reduction of numerous electron acceptors has been extensively studied in connection with the conversion of quinone drugs and xenobiotics in microsomes into reactive semiquinones, capable of inducing damaging effects in humans. (In 1980s, the microsomal reduction of anticancer anthracycline antibiotics and related compounds were studied in detail due to possible mechanism of their cardiotoxic activity and was discussed by us earlier [37], It has been shown that semiquinones of... 

Hydroxyurea interferes with the synthesis of both pyrimidine and purine nucleotides (see table 23.3). It interferes with the synthesis of deoxyribonucleotides by inhibiting ribonucleotide reductase of mammalian cells, an enzyme that is crucial and probably rate-limiting in the biosynthesis of DNA. It probably acts by disrupting the iron-tyrosyl radical structure at the active site of the reductase. Hydroxyurea is in clinical use as an anticancer agent. 

It was found that dihydroartemisinin can selectively kill cancer cells in the presence of holotransferrin, which can increase intracellular iron concentrations, and normal breast cells (HTB 125) and lymphocytes had nonsignificant changes. It seems the mechanisms of anticancer action and of antimalarial activity are similar.2 -" ... 

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