title: Selective speciation improves efficacy and lowers toxicity of platinum anticancer and vanadium antidiabetic drugs.
abstract: Improving efficacy and lowering resistance to metal-based drugs can be addressed by consideration of the coordination complex speciation and key reactions important to vanadium antidiabetic drugs or platinum anticancer drugs under biological conditions. The methods of analyses vary depending on the specific metal ion chemistry. The vanadium compounds interconvert readily, whereas the reactions of the platinum compounds are much slower and thus much easier to study. However, the vanadium species are readily differentiated due to vanadium complexes differing in color. For both vanadium and platinum systems, understanding the processes as the compounds, Lipoplatin and Satraplatin, enter cells is needed to better combat the disease; there are many cellular metabolites, which may affect processing and thus the efficacy of the drugs. Examples of two formulations of platinum compounds illustrate how changing the chemistry of the platinum will result in less toxic and better tolerated drugs. The consequence of the much lower toxicity of the drug, can be readily realized because cisplatin administration requires hospital stay whereas Lipoplatin can be done in an outpatient manner. Similarly, the properties of Satraplatin allow for development of an oral drug. These forms of platinum demonstrate that the direct consequence of more selective speciation is lower side effects and cheaper administration of the anticancer agent. Therefore we urge that as the community goes forward in development of new drugs, control of speciation chemistry will be considered as one of the key strategies in the future development of anticancer drugs.
authors.affiliation: Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Doucette
authors.affiliation: Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Hassell
authors.affiliation: Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA; Dept. Chemistry, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: Debbie.Crans@ColoState.Edu.
authors.forename: Debbie C
authors.initials: DC
authors.lastname: Crans
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D002945:Cisplatin / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000627:therapeutic use; D014639:Vanadium / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D009944:Organoplatinum Compounds; C503131:lipoplatin; D014639:Vanadium; C081294:satraplatin; D002945:Cisplatin
keywords: Anticancer; Antidiabetes; Cisplatin; Coordination chemistry; Speciation; Vanadium