Anticancer Drug Production

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

Bryostatins are another class of compounds that bind to the Cl domain and result in acute activation of PKC. However, unlike phorbol esters, these marine natural products have antitumor effects. Bryostatins are currently in phase II clinical trials and show promise as anticancer drugs, particularly when combined with other adjuvant therapy. 

Stephen Hilton obtained his B.Sc. at King s College London in 1996 followed by a Ph.D. under the supervision of Professor Keith Jones and Dr Sheetal Handa. In 2002 he carried out a postdoctoral fellowship under the supervision of Professor William Motherwell at University College London. In 2006 he moved to his current position at The Institute of Cancer Research as a postdoctoral fellow in Medicinal Chemistry. His research interests lie in the area of natural products containing sulfur, radical chemistry and anticancer drug targets. 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

In the process of identifying the reaction products of the anticancer drug cis-DDP with DNA bases, unusually dark blue compounds were found, which were called platinum-pyrimidine-blues. Interestingly,... 

Because HMG CoA reductase occurs before a branch point in the biosynthetic pathway, complete inhibition of the enzyme by cholesterol would necessarily deprive the cell of many other intermediates, some of which are important in cell growth and division. A group of drugs known as statins are widely used to reduce plasma cholesterol concentration by inhibiting HMG CoA reductase. Interest is now rising in the possible use of statins as anticancer drugs due to their impact on reducing the production of mediators of cell proliferation. 

Monneret C. (2010) Cnrrent impact of natural products in the discovery of anticancer drugs. Ann Pharm Fr 68 218-232. 

Butler MS, Newman DJ. (2008) Mother nature s gifts to diseases of man The impact of natural products on anti-infective, anticholestemics and anticancer drug discovery. Prog Drug Res 65 3 44. 

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