Screening drugs derived from

TABLE 7.1 Drugs Derived from Screening Leads ... 

IV. EXAMPLES OF DRUGS DERIVED FROM SCREENING LEADS... 

The highly significant work done in connection with Taxol illustrates the importance of screening natural sources for possible medically useful and active compounds. It stresses the need for international cooperation in the preservation of natural resources and collaboration in the identification, development and testing of potential new pharmaceuticals and other chemicals. Natural products are compounds isolated from natural sources and include Taxol, mescaline and capsaicin. Many of the drugs derived from natural sources are chiral, including nicotine, dopamine, thyroxine and naproxen, and this is the topic we now move on to consider. 

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]. 

Screening a large pharmaceutical library derived from eukaryotic drug discovery programs afforded pyridopyrimidine 2, a lead targeting the... 

The selection of building blocks is based on information derived from, for example, computational chemistry, where potential virtual ligand molecules are modeled to fit the receptor-protein binding site. Combinatorial chemistry commences with a scaffold or framework to which additional groups are added to improve the binding affinity. Compounds are prepared and later screened using HTS. In this way, many compounds are tested within a short time frame to speed up drug discovery. 

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