Podophyllum peltatum podophyllotoxin derivatives

Podophyllotoxin is extracted from the mandrake plant. Podophyllum peltatum. A derivative of this chemical, etoposide, is used in small cell lung cancer, lymphoma and testicular cancer. The mode of action of etoposide is not completely known, but it may be due to an inhibitory effect on topoisomerase similar to that of doxombicin (see above). 

Two compounds, VP-16 (etoposide) and a related drug, VM-26 (teniposide), are semisynthetic derivatives of podophyllotoxin, which is extracted from the mayapple root (Podophyllum peltatum). Both an intravenous and an oral formulation of etoposide are approved for clinical use in the USA. 

To obtain the high-pure compounds from the candidate total extracts, column chromatographic separation is performed for some illustrative total extracts. For example, squalene and podophyllotoxin with high purity are isolated from the related extracts. Upon comparison with the LSE, we found that squalene can be easily obtained from the SFE extract than the case of LSE. Although we are not shown here similar interesting results are obtained for other substances. For example, high-purity podophyllotoxin derivatives, which has been known for antitumor activity[4] can be obtained easily from the SFE extract of Podophyllum peltatum. 

Important drugs have been derived from two plants common in the woodlands of the eastern United States. One is etoposide (an anticancer drug) based on the podophyllotoxin found in Podophyllum peltatum,415 The second is sanguinarine (from Sangulnarla canadensis), which is used for treatment of periodontal disease. A common fence lizard of the western United States, Sceloporus occidentalis, has something in the blood that kills the bacteria responsible for Lyme disease.416... 

The epipodophyllotoxins (Fig. 42.38) are semisynthetic glycosidic derivatives of podophyllotoxin, the major component of the resinous podophyllin isolated from the dried roots of the American mandrake or mayapple plant (Podophyllum peltatum). Although these compounds are capable of binding to tubulin and inhibiting mitosis, their primary mechanism of antineoplastic action is poisioning topoisomerase II, a mechanism that they share... 

Kutney et al. have studied the production of podophyllotoxin derivatives using cultures of Podophyllum peltatum and Catharanthus roseus [126-128X In particular they have established procedures for the biotransformation of readily prepared dibenzylbutyrolactones into podophyllotoxin derivatives using a semi-continuous fermentation process (scheme 58). However, even here the major products obtained belong to the 1,2-trans- (isopodophyllotoxin) series. 

Podophyllotoxin (5./7), from Podophyllum peltatum, the tropical squirting cucumber , strongly inhibits the polymerization of tubulin and is used in dermatology to destroy warts and other skin neoplasms. Deoxy-podophyllo-toxin, from the berries of the juniper tree, has anti-viral activity. Etoposide, a semi-synthetic derivative of podophyllotoxin, is used clinically for the treatment of otherwise fatal tumours. Chemically it is demethyl-1-0-(4,6-0-ethylidene-)8-D-glucopyranosyl)epipodophyllotoxin. It does not seem to prevent the synthesis of microtubules, but a decrease in DNA synthesis is noted (Loike, 1984). 

A strong cytotoxic lignan is podophyllotoxin (Fig. 17) irom Podophyllum peltatum or P. hex-andrum (Berberidaceae). Podophyllotoxin has the same mechanism of action as the terpene indole alkaloids vinblastine and vincristine it inhibits cell division by binding to tubulin and preventing its polymerization. This lignan is used as treatment for warts, but is too toxic for systemic application. Derivatives with reduced toxicity are etoposide, etopophos, and tenipo-side. They are prepared semi-synthetically from 4 -demethylpodophyllotoxin and have an inverted stereochemistry at C-4. These changes lead to a new anticancer mechanism, the... 

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