Etoposide antitumor natural product

Although not listed in the tables, at least four other natural product drugs have given yeoman service in the antitumor area. The first of these is paclitaxel (Taxol ) which sold US 1.6 billion in 2000 this is followed by the vinca alkaloids vinblastine and vincristine. Completing the quartet are the natural product-derived epi-podophyllotoxin derivatives teniposide and etoposide and the materials derived from camptothecin, topotecan and CPT-11. These will probably not be the only natural product drugs in the antitumor field, as can be seen by inspection of Table 6.3, where Cragg and Newman recently reported on the source... 

Podophyllotoxin 3 is a naturally occurring antitumor antibiotic . Attempts to reduce the toxicity have resulted in the synthesis of glucosidic phenolic derivatives, VP-16 (etoposide, a semisynthetic analog) 4a and VM-26 (teniposide) 4b. Their mode of action is thought to be associated with DNA breakage . Haim et al. proposed a mechanistic pathway entailing oxidation with subsequent 0-demethylation to form the o-quinone metabolite 5a (Equation 2). In vivo conversion of methoxyl to hydroxyl has been previously observed . Electrochemical oxidation of VP-16 and other methoxyphenols also leads to quinone products. 

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