A chemical perspective on the clinical use of platinum-based anticancer drugs

Abstract

Chemists have a key role to play in the clinical use and improvement of platinum anticancer drugs with regard to preclinical testing, formulation, pharmacokinetics, and drug–drug interactions.

Oral Anticancer Heterobimetallic PtIV−AuIComplexes Show High In Vivo Activity and Low Toxicity

“…The multi‐action agent approach is dominant in the field of Pt anticancer agents primarily because inert octahedral Pt IV complexes are exceptionally well suited to act as multi‐purpose prodrugs that are activated by reduction inside the cancer cells, simultaneously releasing FDA‐approved square planar Pt II drugs [cisPt and oxaliplatin (oxaliPt)—Figure 1A and 1B] and up to two additional (bioactive) moieties in the axial positions (Figure 1C). [6] Pt II complexes have been used worldwide for more than 50 years to treat cancer, mostly in combination with other anticancer drugs [7] . Their mechanism of action is based on the formation of intra‐strand crosslinks preferentially between N7 of guanine DNA bases resulting in the induction of apoptosis [8] .…”

“…[6] Pt II complexes have been used worldwide for more than 50 years to treat cancer, mostly in combination with other anticancer drugs. [7] Their mechanism of action is based on the formation of intra-strand crosslinks preferentially between N7 of guanine DNA bases resulting in the induction of apoptosis. [8] They suffer from inherent or acquired resistance as well as their dose-limiting side effects, such as nephrotoxicity, neurotoxicity, and ototoxicity.…”

A trans-Pt(ii) hedgehog pathway inhibitor complex with cytotoxicity towards breast cancer stem cells and triple negative breast cancer cells

“…1, are administered singularly or in anticancer regimens together with other anticancer agents such as doxorubicin, etoposide, gemcitabine, paclitaxel and 5-fluorouracil. 2 The cytotoxicity of Pt anticancer drugs is primarily attributed to electrophilic Pt(II) centres covalently binding nuclear DNA, which induces DNA perturbation damage responses and ultimately programmed cell death, apoptosis. Pt(II) centres are also increasingly accepted to react with many cytoplasmic nucleophiles, including mitochondrial DNA, RNA as well as multiple mitochondrial and extramitochondrial proteins.…”

“…1, are administered singularly or in anticancer regimens together with other anticancer agents such as doxorubicin, etoposide, gemcitabine, paclitaxel and 5-fluorouracil. 2…”

Theoretical investigation of triplet potential energy surfaces for (C^C*) cyclometalated platinum(ii) complexes and the corresponding control strategies

“…In the application of anticancer drugs, previous studies report that some derivatives have been conjugated to Pt(II) drugs to elicit promising anticancer effects. [1][2][3][4][5][6] The oxaliplatin scaffold was chosen based on the findings that tetracarboxylato Pt(IV) compounds are generally stable toward reduction. 7,8 This prodrug supposedly exists in its intact Pt(IV) form in the dark but is activated to release oxaliplatin and PPA under the irradiation of red light.…”