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Anticancer Metal Compounds

How metal compounds can be used as anti-cancer agents

Metal compounds such as Platinum, Cobalt and Ruthenium are used as anticancer agents. Anticancer metal compound research is important as chemotherapy is not selective, being very toxic to patients damaging normal DNA cells. Such metal compounds act as anti-cancer agents with the metals being able to vary in oxidation states. 


Selectivity of metal compounds to target only cancer cells arises from the metals properties of varying oxidation states for redox reactions. As cancer exists in hypoxic environments, the oxidation state of the metal is able to vary releasing the cancer drug only in the cancer environment. For example prodrugs are relatively inert metal complexes with relatively high oxidation states.  PtIV, and CoIII are selective carriers undergoing reduction by varying the metals oxidation state in cancerous hypoxic environments releasing anticancer drugs. CoIII reduced to CoII, PtIV reduced to PtII  in hypoxic environments. CoIII two oxidation states: Cobalt (III) is kinetically inert with low-spin 3d6 configuration, CoII is labile (high-spin 3d7). When CoIII is reduced to CoII in hypoxic environments, the active molecule is released then restored to its active form killing cancer cells. Cobalt can also bind to ligands like nitrogen mustards and curcumin ligands, exhibiting redox reactivity for cancer therapy. Nitrogen mustards are highly toxic due to their DNA alkylation and cross-linking activity. In vivo they are not selective for tumour tissue however can be deactivated by coordination to CoIII, released on reduction to CoII in hypoxic tumour tissue. This reduces systemic toxicity concluding an efficient anticancer drug.


Platinum anticancer metal compounds treat ovarian, cervical and neck cancer. Platinum (PtIV) (cisplatin) exhibits redox-mediated anticancer activity, highly effective towards tumours. Platinum causes severe side-effects for patients so PtIV prodrug is used selectively reducing tumour sites.


Ruthenium is used for cancer therapy as a less toxic metal over platinum. Ruthenium targeted therapy selectively disrupts specific cellular pathways where cancer cells rely for growth and metastasis. Reduction of Ru (III) to Ru(II) selectively occurs in hypoxic reducing environments where tumours over express transferrin receptors, ruthenium binding to.


Overall metal compounds for cancer treatment attracted high interest due to redox activity properties. Metal compounds are selective to cancer cells, limiting patients' side effects. Such therapy shows how inorganic chemistry is important to medicine. 



By Alice Davey

 

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