Monofunctional Platinum (PtII) Compounds – Shifting the Paradigm in Designing New Pt-based Anticancer Agents

Author(s): Shu Xian Chong, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To.

Journal Name: Current Medicinal Chemistry

Volume 23 , Issue 12 , 2016

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Abstract:

Platinum (Pt)-based anticancer drugs, exemplified by cisplatin, are key components in combination chemotherapy. However, their effective use is hindered by toxicity and emergence of drug resistance. They bind to DNA and mainly form the Pt-GG diadduct, subsequently leading to apoptosis to mediate cell death. On the other hand, the Pt drug –proteins and –metabolites interactions, which involve the reaction between Pt and sulfur sites located in protein side chains and important bionucleophiles (e.g., glutathione), are responsible for the toxicity and drug resistance problem. Therefore, carefully designed coordinating ligands may provide the means of fine tuning the electronic environment around the core Pt atom and allow the resulting Pt compounds to bind with the DNA in a different manner. This may produce alternative cell death mechanisms in cancer cells, thereby circumventing Pt resistance. This article reviewed the recent development in monofunctional Pt complexes and their prospects in becoming a new generation of anticancer drugs.

Keywords: Cisplatin, carboplatin, oxaliplatin, platinum drug, monofunctional platinum drug.

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Article Details

VOLUME: 23
ISSUE: 12
Year: 2016
Page: [1268 - 1285]
Pages: 18
DOI: 10.2174/0929867323666160311114509
Price: $58

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