Natural Products in Chemical Biology

13

NATURAL PRODUCTS AS ANTICANCER AGENTS

DAVID G. I. KINGSTON

Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia

DAVID J. NEWMAN

Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland

Natural products have provided some of the most effective drugs for the treatment of cancer, including such well-known drugs as paclitaxel (Taxol™; Bristol-Myers Squibb) adriamycin, vinblastine, and vincristine. Natural products have also provided many compounds that have led to the discovery of new biochemical mechanisms. This review summarizes the major natural products in clinical use today and introduces several new ones on the cusp of entering clinical practice. The review is organized by mechanism of action, with compounds that interact with proteins discussed first, followed by compounds that interact with RNA or DNA.

Natural products were the original source of almost all the drugs used by mankind before 1900, and they continue to be a major source of new drugs and drug leads (1, 2). The reasons for the continued importance of natural products are not hard to discover. In the first place, a high correlation exists between the properties of drugs and those of natural products (3, 4). In addition, natural products usually have built-in chirality, and they are thus uniquely suited to bind to complex proteins and other biologic receptors. Finally, natural ...