DNA DAMAGE MECHANISMS OF ANTI-CANCER DRUGS

Abstract

Organic molecules with DNA-damage ability are of great potential in the development of medicine, toxicology, biochemistry, organic chemistry, biotechnology and gene therapy. DNA damaging agents have historically played a central role in cancer therapy. Even as new approaches to cancer therapy become available, it seems likely that there will be a continued need for the study and development of novel DNA damaging cytotoxins. These agents will see continued use due to their well-establised role in treating various types of cancer and because many of the new approaches to cancer treatment such as immunoteraphy and modulation of the cell cycle are most effective when used in combination with traditional cytotoxins. It is commonly believed that natural products which display potent biological activity are results of natural selection. DNA-damaging natural products frequently possess potent cytotoxic, cytostatic or mutagenic properties and, in nature, may serve as either offensive or defensive weapon in the struggle for survival. Natural products constitute a vast library of organic compounds that can serve as a useful force. A practical reason for the longstanding interest in DNA-damaging natural products is the fact that the cytotoxic or cytostatic effects of these agents sometimes endow them with useful medicinal properties, especially as potential anticancer therapeutics. Several DNA-damaging natural products are currently in use for the treatment of various cancers and others have served as lead compounds in the development of therapeutic agents. Many anti-cancer agents work by alkylating DNA while others destroy DNA by radical chemistry, starting either (i) by abstracting a hydrogen atom from a deoxyribose sugar or (ii) by adding to the alkene pi bond in a base.DNA-damaging agents can be placed into four chemical categories: Intercalators, alkylating agents, DNA strand breakers and groove binders. In this review, DNA damage mechanisms of anti-cancer drugs are 33

discussed.Finally, natural products with extremely potent biological activities sometimes reveal unforeseen biological pathways and these compounds can become useful tools for elucidating the details of complex life processes.

Keywords

• Natural Products,DNA Damage,Anti-Cancer Agents

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