Understanding how the platinum anticancer drug carboplatin works: From the bottle to the cell

Anthony J. Di Pasqua, Jerry Goodisman, James C. Dabrowiak

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer-dimer equilibrium with an association constant of K (M -1) ≈ 391, a property that accounts for the long-term stability of its ready-to-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO 3 2- (k 1 = 2.04 ± 0.81 × 10 -6 in 24 mM carbonate buffer, pH 7.5 at 37 °C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalInorganica Chimica Acta
Volume389
DOIs
StatePublished - Jul 1 2012

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bottles
Carboplatin
Bottles
Platinum
Carbonates
drugs
platinum
carbonates
Biological systems
cells
Pharmaceutical Preparations
Chemical activation
Ligands
Cisplatin
Nucleophiles
carbonic acid
activation
Carbonic Acid
ligands
biological effects

Keywords

  • Carbonate
  • Carboplatin
  • Mechanism of action
  • Self-association

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Materials Chemistry

Cite this

Understanding how the platinum anticancer drug carboplatin works : From the bottle to the cell. / Di Pasqua, Anthony J.; Goodisman, Jerry; Dabrowiak, James C.

In: Inorganica Chimica Acta, Vol. 389, 01.07.2012, p. 29-35.

Research output: Contribution to journalArticle

Di Pasqua, Anthony J. ; Goodisman, Jerry ; Dabrowiak, James C. / Understanding how the platinum anticancer drug carboplatin works : From the bottle to the cell. In: Inorganica Chimica Acta. 2012 ; Vol. 389. pp. 29-35.
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