Camptothecin chemical structures

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]. 

Camptothecin is highly insoluble, which facilitated its crystallization and chemical structure determination. 

Akimoto K, Akiko K, Ohya K, Sawada S, Aiyama R. Photodegradation reactions of GPT-11, a derivative of camptothecin 11 chemical structure of main degradation products in aqueous solution. Drug Stab 1997 1 118-122. 

Among the worldwide total of 30000 known natural products, about 80% stems from plant resources. The number of known chemical structures of plant secondary metabolites is four times the number of known microbial secondary metabolites. Plant secondary metabolites are widely used as valuable medicines (such as paclitaxel, vinblastine, camptothecin, ginsenosides, and artemisinin), food additives, flavors, spices (such as rose oil, vanillin), pigments (such as Sin red and anthocyanins), cosmetics (such as aloe polysaccharides), and bio-pesticides (such as pyrethrins). Currently, a quarter of all prescribed pharmaceuticals compounds in industrialized countries are directly or indirectly derived from plants, or via semi-synthesis. Furthermore, 11% of the 252 drugs considered as basic and essential by the WHO are exclusively derived from plants. According to their biosynthetic pathways, secondary metabolites are usually classified into three large molecule families phenolics, terpenes, and steroids. Some known plant-derived pharmaceuticals are shown in Table 6.1. 

Figure 8.7 Chemical structures of camptothecin, irinotecan, and topotecan.

Camptothecine, C20H16O4N2 (mp 264°-267° [a]f( +31.3°) was shown to have inhibitor activity against both lukemia and tumors. Exhaustive spectral analysis, finally by X-ray methods, showed that it had structure XXVI. The formation of several crystalline derivatives by the known chemical reactions was consistent with this structure (38). 

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