Antitumor lignans podophyllotoxins

In recent decades, a number of antitumor lignans have been synthesized, and their structure-activity correlations have been reported. Ring-A-opened podophyllotoxin lignans were synthesized by Michael Initiated Ring Closure (MIRC). Compound 67 showed the strongest inhibition of DNA topoisomerase II like 65 [55]. Naturally... 

The best example of a lignan used as a lead compound is podophyllotoxin, an antimitotic compound that binds to tubulin, although podophyllotoxin has not been isolated from Taxus species,. Etoposide and teniposide are well-known compounds derived from podophyllotoxin, and their antitumor activity is due to the inhibition of topoisomerase II. 

At least 40 lignans are known to have antitumor and antiviral activity and many are cytotoxic (Ayres and Loike, 1990 Davin et al., 1992 MacRae and Towers, 1984 Mac-Rae et al., 1989), although there are no common structural features to explain this activity. Podophyllotoxin (51) (Fig. 8.15), which has been isolated from a number of plant species, is a potent antineoplastic (i.e., tumor destructive) compound. Although too toxic for practical value, synthetically... 

Podophyllin has strong cathartic and antineo-plastic properties. These properties are due to the lignans and their glucosides present, with the former being more potent. The cathartic properties are reported to be due mainly to the peltatins, while the antitumor properties are attributed to podophyllotoxin and 4-demethyl-podophyllotoxin as well as the peltatins. ... 

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