鬼臼毒素, Podophyllotoxin

Podophyllotoxin is an alcohol derivative that can be found in the rhizome and roots of the perennial plant Podophyllum peltatum. It is a cytotoxic agent that binds to DNA and inhibits protein synthesis. It has been shown to induce oxidative stress and cell death in cancer cells. Podophyllotoxin has also been shown to have anti-cancer effects in leukemia and other cancers, as well as being a potential anticancer drug for acute leukemia. Podophyllotoxin is a cytotoxic agent that binds to DNA and inhibits protein synthesis. It has been shown to induce oxidative stress and cell death in cancer cells. Podophyllotoxin has also been shown to have anti-cancer effects in leukemia and other cancers, as well as being a potential anticancer drug for acute leukemia.

Potent, competitive microtubule assembly inhibitor (IC50 = 5 μM). Prevents the formation of mitotic spindles. Antitumor and keratolytic agent. Active in vivo and in vitro. Cell-permeable derivative, etoposide, also available.

Podophyllotoxin is a lignan that has been found in Podophyllum and has diverse biological activities. It inhibits polymerization of isolated chicken brain tubulin (IC50 = 0.6 µM) and induces mitotic arrest at the G2/M phase in CCRF CEM lymphoblastic leukemia cells when used at concentrations ranging from 0.01 to 5 µg/ml. Podophyllotoxin (5 µM) is protective against herpes simplex virus 1 (HSV-1) infection in Vero cells. It inhibits the proliferation of several diffuse large B cell lymphoma (DLBCL) cell lines (IC50s = 0.0098-0.017 µM). Podophyllotoxin is a starting material in the semisynthesis of the anticancer compounds etoposide and teniposide. Formulations containing podophyllotoxin have been used in the treatment of external genital warts.

(-)-Podophyllotoxin analytical standard provided with w/w absolute assay, to be used for quantitative titration.

Podofilox is a pure, stabilized form of podophyllin, in which only the biologically active portion of the compound is present. Podophyllotoxin is a toxic, polycyclic antimitotic agent isolated primarily from the rhizome of the plant Podophyllum peltatum. This agent is formulated for topical applications. (NCI04)

Podofilox, also known as condylox or podophyllotoxin, belongs to the class of organic compounds known as podophyllotoxins. These are tetralin lignans in which the benzene moiety of the tetralin skeleton is fused to a 1, 3-dioxolane and the cyclohexane is fused to a butyrolactone (pyrrolidin-2-one). Podofilox is a drug which is used for treatment of external genital warts (condyloma acuminatum). Podofilox exists as a solid and is considered to be practically insoluble (in water) and relatively neutral. Podofilox has been detected in multiple biofluids, such as urine and blood. Within the cell, podofilox is primarily located in the cytoplasm and membrane (predicted from logP). Podofilox can be converted into etoposide and teniposide. Podofilox is a potentially toxic compound.

The physiologic effect of podofilox is by means of Decreased Mitosis.

Title: Podophyllotoxin

CAS Registry Number: 518-28-5

CAS Name: (5R,5aR,8aR,9R)-5,8,8a,9-Tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)furo[3¢,4¢:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one

Additional Names: 1-hydroxy-2-hydroxymethyl-6,7-methylenedioxy-4-(3¢,4¢,5¢-trimethoxyphenyl)-1,2,3,4-tetrahydronaphthalene-3-carboxylic acid lactone; podophyllinic acid lactone; podofilox

Trademarks: Condyline (Nycomed); Condylox (Oclassen); Wartec (Kabi); Warticon (Perstorp)

Molecular Formula: C22H22O8

Molecular Weight: 414.41

Percent Composition: C 63.76%, H 5.35%, O 30.89%

Literature References: Precursor of antineoplastics etoposide, teniposide, q.q.v. Found in the rhizomes of North American Podophyllum peltatum L., Podophyllaceae: V. Podwyssotski, Arch. Exp. Pathol. Pharmakol. 13, 29 (1880); also in P. emodi Wall.: von Wartburg et al., Helv. Chim. Acta 40, 1331 (1957); in Juniperus virginiana L., Cupressaceae: Kupchan et al., J. Pharm. Sci. 54, 659 (1965). Structure and absolute configuration: Schrecker, Hartwell, J. Org. Chem. 21, 381 (1956). Crystal structure: T. J. Petcher et al., J. Chem. Soc. Perkin Trans. 2 1973, 288. Synthesis: Gensler, Gatsonis, J. Am. Chem. Soc. 84, 1748 (1962); T. Kaneko, H. Wong, Tetrahedron Lett. 28, 517 (1987). Asymmetric total synthesis: R. C. Andrews et al., J. Am. Chem. Soc. 110, 7854 (1988); E. J. Bush, D. W. Jones, Chem. Commun. 1993, 1200. Toxicity data: F. S. Phillips et al., Fed. Proc. 7, 249 (1948). ELISA determn in plants: K.-J. Yoo, J. R. Porter, J. Nat. Prod. 56, 715 (1993). Clinical evaluation for treatment of genital warts: A. Lassus, Lancet 2, 513 (1987); K. R. Beutner et al., ibid. 1, 831 (1989). Review of early literature: Hartwell, Schrecker in Fortschr. Chem. Org. Naturst. 15, 98-121 (1958). Review of chemistry and antineoplastic activity: I. Jardine, Anticancer Agents Based on Natural Product Models, J. M. Cassady, J. D. Douros, Eds. (Academic Press, New York, 1980) pp 319-351. Review of syntheses: R. S. Ward, Synthesis 1992, 719-730. Review: D. L. Sackett, Pharmacol. Ther. 59, 163-228 (1993).

Properties: Solvated crystals. mp 114-118° (effervescence). Several polymorphic modifications. After drying: mp 183.3-184.0°. [a]D20 -132.7° (chloroform). Soly in water at 23°: 120 mg/l. Sol in alcohol, chloroform, acetone, warm benzene, glacial acetic acid. LD50 in rats (mg/kg): 8.7 i.v.; 15 i.p. (Phillips).

Melting point: mp 114-118° (effervescence); mp 183.3-184.0°

Optical Rotation: [a]D20 -132.7° (chloroform)

Toxicity data: LD50 in rats (mg/kg): 8.7 i.v.; 15 i.p. (Phillips)

Derivative Type: Podophyllotoxin-b-D-glucoside

Molecular Formula: C28H32O13

Molecular Weight: 576.55

Percent Composition: C 58.33%, H 5.59%, O 36.08%

Properties: Hygroscopic amorphous white flakes, mp 152-154°. [a]D20 -76.4° (c = 0.576 in methanol); [a]D20 -117.0° (c = 0.668 in pyridine).

Melting point: mp 152-154°

Optical Rotation: [a]D20 -76.4° (c = 0.576 in methanol); [a]D20 -117.0° (c = 0.668 in pyridine)

Derivative Type: Picropodophyllin

CAS Registry Number: 477-47-4

Additional Names: Picropodophyllinic acid lactone

Molecular Formula: C22H22O8

Molecular Weight: 414.41

Percent Composition: C 63.76%, H 5.35%, O 30.89%

Literature References: Found in resin podophyllum, a dried alcoholic extract of Podophyllum peltatum L., Berberidaceae but not in the fresh plant. 5aS-Isomer of podophyllotoxin. Isoln from resin podophyllum: Späth et al., Ber. 65, 1545 (1932). Structure: Schrecker, Hartwell, J. Am. Chem. Soc. 76, 752 (1954). Synthesis: Gensler, Wang, J. Am. Chem. Soc. 76, 5890 (1954); Gensler et al., ibid. 82, 1714 (1960).

Properties: Crystals from acetone. Irritates the skin. mp 214°. Higher-melting modification from abs ethanol, mp 228°. [a]D20 +9.4° (c = 0.7 in chloroform). Soly in water at 25° ~100 mg/l. Fairly sol in chloroform, hot ethanol, acetic acid, acetone, dil caustic; less sol in benzene, ether, carbon tetrachloride, propylene glycol. Practically insol in petr ether.

Melting point: mp 214°; mp 228°

Optical Rotation: [a]D20 +9.4° (c = 0.7 in chloroform)

Therap-Cat: Antiviral (topical).

Keywords: Antiviral.