Podophyllin Podophyllotoxin

Podocarp-8(14)-en-15-oic acid, 13a-methyl-13-vinyl-. See Pimaric acid Podophyllin Podophyllotoxin Podophyllum. See Podophyllum resin Podophyllum resin... 

Podophyllum Basin. U.S.P. (Podophyllin) is prepared from the dried rhizome and roots of Podophyllum peltatum (may apple, mandrake), a plant used by native peoples. An amorphous greenish-yellow powder, with a slight peculiar odor and faintly bitter taste, its active constituents are a resin and a crystalline principle, podophyllotoxin. The dose of the resin is 0.01 to 0.065 g, 1/6 to 1 grain. It is very irritating to mucous membranes, especially of the eyes. 

Podophyllotoxin 1-0-glucoside (= Podophyllinic acid lactone 1-0-glucoside) (lignan)... 

The first chemical constituent was isolated from podophyllin in 1880 and named podophyllotoxin (97). A structure was proposed in 1932 and after some fine-tuning (98) was shown to be the lignan (60). As might be expected, the crude resin contains a variety of chemical types, including the flavonols quercetin and kaempferol (99). Although these other constituents undoubtedly have biological activity, it is the lignans that have received most attention and to which we shall devote the remainder of this section. 

Etoposide and teniposide are semisynthetic podophyllotoxin derivatives (see Table 124-13). Podophyllin is extracted from the mayapple or mandrake plant. Like the vinca alkaloids, podophyllin itself binds to tubulin and interferes with microtubule formation. Unlike the parent compound, however, etoposide and teniposide damage tumor cells by causing strand breakage through inhibiting topoisomerase Resistance may be caused by differences in topoisomerase II levels, by increased cell ability to repair strand breaks, or by increased levels of P-glycoproteins. Etoposide and teniposide are usually clinically cross-resistant. They are cell-cycle phase-specific and arrest cells in... 

Podophyllotoxin (1), 4 -danethyldeoxypodophyUotoxin (2) and P-apopicro-podophyllin (3) strongly inhibited P-388 (murine lymphocytic leukemia) the IC50 values (concentration at which 50% of cells were killed) were 0.003, 0.005, and... 

The resin product obtained by extraction of the dried roots and rhizomes of the North American plant Podophyllum peltatum L. (the American mandrake or mayapple) and of the related Indian species Podophyllum emodi Wall. Ex Royle is known as podophyllin and has long been known to possess medicinal properties. The major active substance in podophyllin is the lignan lactone podophyllotoxin (7) although a variety of other lignans and lignan glycosides have also been isolated from podophyllin. ... 

Podophyllum resin Podophylline MD Only aglycones due to extraction procedures >20% podophyllotoxin, (X-, (3-pellatines, desoxy and dehydropo dophyll i ne ... 

Podophyllin (podophyllum resin) is a mixture of chemicals from the plant Podophyllum peltatum (mandrake or May apple). The major constituent of the resin is podophyllotoxin (podofilox). It binds to microtubules and causes mitotic arrest in metaphase. Podophyllum resin (10 0%) is applied and left in place for 2-6 hours weekly for the treatment of anogenital warts. Irritation and ulcerative local reactions are the major side effects. It should not be used in the mouth or during pregnancy. Podofilox (CONDYLOX, others) is available as a 0.5% solution for application twice daily for 3 consecutive days. Weekly cycles may be repeated. 

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... 

Case reports and animal studies have indicated that compounds from Himalayan mayapple have abortifacient activity (Chamberlain et al. 1972 Didcock et al. 1952 Longstaff and von Krogh 2001). A safety assessment of the compounds podophyllotoxin and podophyllin indicated that the topical use of these compounds during pregnancy is strongly contraindicated (Longstaff and von Krogh 2001). 

The LD50 of a fractionated extract (with podophyllin and podophyllotoxin removed) of Himalayan mayapple in mice is 250 mg/kg after oral administration and 90 mg/kg after intraperitoneal administration (Gupta et al. 2008a, 2008b Lata et al. 2009). 

Longstaff, E., and G. von Krogh. 2001. Condyloma eradication Self-therapy with 0.15 -0.5% podophyllotoxin versus 20-25% podophyllin preparations—an integrated safety assessment. Regul. Toxicol. Pharrtmml. 33(2) 117-137. 

Podophyllin or podophyllum resin is the alcohol-soluble and water-insoluble resinous material present in podophyllum in 3-6%. Due to the method of preparation, podophyllin generally contains little or no lignan glucosides. Most of the active principles present are the lignan aglycones consisting of about 20% podophyllotoxin, 13% P-peltatin,... 

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. ... 

Podophyllin and podophyllotoxin have been demonstrated to be strongly embryocidal and growth retarding but not teratogenic in animals (e.g., mice and rats). ... 

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