Abstract
Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation reaction kinetics) that determine site-specific toxicity; second, the impact on RNA molecules. Knowledge of the ‘RNA world’ has dramatically changed our understanding of cellular and molecular biology. The inherent RNA-crosslinking properties should make platinum-based drugs interact with coding and non-coding RNAs. Third, we will discuss the impact on the immune system, which is now recognized to substantially contribute to chemotherapy efficacy. Together, platinum drugs are in fact old drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave the way to new drugs or an improved application of the already existing compounds.
Highlights
Oxaliplatin, and carboplatin belong to the most prominent antineoplastic drugs used against a broad set of solid malignancies
Most—but not all [1]—review articles concentrate on the DNA platination-mediated effects, with good cause, because the structural and functional disturbances of genomic or mitochondrial DNA seem to be at the bottom of platinum drug pharmacology
The platinum drugs differ with respect to systemic and cellular pharmacodynamics, pharmacokinetics, and toxicity [3,4,5]
Summary
Oxaliplatin, and carboplatin belong to the most prominent antineoplastic drugs used against a broad set of solid malignancies. Molecules 2017, 22, 382 substitution with water, the positively charged molecules are nucleophilically targeted by the free electrons of the N7 atom of purines to form intrastrand and interstrand adducts [2] Despite this fundamental conformity, the platinum drugs differ with respect to systemic and cellular pharmacodynamics (concentration-effect relationship), pharmacokinetics (relationship between time and concentration at a certain site), and toxicity [3,4,5]. It reminds us that neither the dose, nor the plasma exposure (AUCp ) or tissue exposure to the parent compound determines toxicity, but that activation kinetics (khydrolysis ) matters since it is the active compound of a drug that causes pharmacological (side) effects (Figure 1) This suggests that through prudent selection of respective leaving groups, platinum drugs can be designed to exhibit particular pharmacological characteristics.
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