Biomolecular Targets for Platinum Antitumor Drugs

Author: Bose R.N.

Source: Mini Reviews in Medicinal Chemistry, Volume 2, Number 2, April 2002 , pp. 103-111(9)

Publisher: Bentham Science Publishers

Abstract:

Cis-diamminedichloroplatinum(II) (cisplatin) is widely used for the treatment of testicular, ovarian, and other forms of cancer. Several second generation platinum centered antitumor drugs have been approved or undergoing phase-3 clinical trial. Cisplatin arrests the cell cycle at the G2 phase by a mechanism commonly known as apoptosis. At the molecular level, it is generally believed that the anticancer properties of these compounds are due to the covalent binding to DNA. In addition to DNA binding, the platinum drugs bind and interact with proteins and enzymes. The toxic effects of the drugs have been usually attributed to protein binding. However, a growing body of work points to much more complex anticancer mechanisms involving direct and indirect interactions of platinum compounds with proteins and enzymes. In this review, a discussion on the strength and weaknesses of DNA binding mechanism followed by enzymes and protein interactions with the drugs are presented for the comprehensive understanding of apoptosis. The purpose of this review is to encourage researchers to explore metallobiochemistry of platinum drugs focusing attention to cellular and molecular events beyond DNA binding.

Keywords: cisplatin; dna polymerases

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389557024605500

Publication date: 2002-04-01

• The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines.
  
  The scope of Mini-Reviews in Medicinal Chemistry will cover all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies.
  
  Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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• In this Subject: Chemistry (General) ,  Pharmacology
• By this author: Bose R.N.

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