Cisplatin: The first metal based anticancer drug.

Authors:
Sumit Ghosh
Sumit Ghosh
North Dakota State University
United States

Bioorg Chem 2019 Apr 11;88:102925. Epub 2019 Apr 11.

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India. Electronic address:

Cisplatin or (SP-4-2)-diamminedichloridoplatinum(II) is one of the most potential and widely used drugs for the treatment of various solid cancers such as testicular, ovarian, head and neck, bladder, lung, cervical cancer, melanoma, lymphomas and several others. Cisplatin exerts anticancer activity via multiple mechanisms but its most acceptable mechanism involves generation of DNA lesions by interacting with purine bases on DNA followed by activation of several signal transduction pathways which finally lead to apoptosis. However, side effects and drug resistance are the two inherent challenges of cisplatin which limit its application and effectiveness. Reduction of drug accumulation inside cancer cells, inactivation of drug by reacting with glutathione and metallothioneins and faster repairing of DNA lesions are responsible for cisplatin resistance. To minimize cisplatin side effects and resistance, combination therapies are used and have proven more effective to defect cancers. This article highlights a systematic description on cisplatin which includes a brief history, synthesis, action mechanism, resistance, uses, side effects and modulation of side effects. It also briefly describes development of platinum drugs from very small cisplatin complex to very large next generation nanocarriers conjugated platinum complexes.

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http://dx.doi.org/10.1016/j.bioorg.2019.102925DOI Listing
April 2019
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