Podophyllotoxin CAS 518-28-5
Introduction：Basic information about Podophyllotoxin CAS 518-28-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Podophyllotoxin Basic information
| Product Name: | Podophyllotoxin |
| Synonyms: | Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-, (5R,5aR,8aR,9R)-;Podophyllotoxin ,98%;(5R)-5,8,8aβ,9-Tetrahydro-9β-hydroxy-5-(3,4,5-trimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aαH)-one;Podophyllotoxin,95%;trimethoxyphenyl)-furo(3',4':6,7)naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;PODOPHYLLIN(RG);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;(5R,5AR,8AR,9R)-9-HYDROXY-5-(3,4,5-TRIMETHOXY-PHENYL)-5,8,8A,9-TETRAHYDRO-5AH-FURO[3',4':6,7]NAPHTHO[2,3-D][1,3]DIOXOL-6-ONE |
| CAS: | 518-28-5 |
| MF: | C22H22O8 |
| MW: | 414.41 |
| EINECS: | 208-250-4 |
| Product Categories: | Anti-virals;Inhibitors;Intermediates & Fine Chemicals;Plant Oils, Toxins, Phenolic Acids & Derivatives;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;CONDYLOX;Non-nucleoside Reverse Transcriptase;Pharmaceuticals;Natural Plant Extract;Microtobule InhibitorsCancer Research;Microtubule Inhibitors;Antitumor Agents;Cell Signaling and Neuroscience;Cytoskeleton and Extracellular Matrix |
| Mol File: | 518-28-5.mol |
Podophyllotoxin Chemical Properties
| Melting point | 183-184 °C (lit.) |
| alpha | -110.7 º (c=1, CHCl3) |
| Boiling point | 453.31°C (rough estimate) |
| density | 1.2649 (rough estimate) |
| refractive index | 1.4480 (estimate) |
| storage temp. | 2-8°C |
| solubility | DMSO:15.0(Max Conc. mg/mL);36.2(Max Conc. mM) |
| form | Powder |
| pka | 13.26±0.40(Predicted) |
| color | White to off-white |
| Optical Rotation | [α]/D 131±2°, c = 1 in chloroform |
| Merck | 13,7628 |
| BRN | 99163 |
| Stability: | Very Hygroscopic |
| InChIKey | YJGVMLPVUAXIQN-XVVDYKMHSA-N |
| SMILES | COc1cc(cc(OC)c1OC)[C@H]2C3C(COC3=O)[C@@H](O)c4cc5OCOc5cc24 |
| LogP | 2.010 |
| CAS DataBase Reference | 518-28-5(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 21-25-36/37/38-23/25-23/24/25 |
| Safety Statements | 36/37/39-45-26 |
| RIDADR | UN 3462 6.1/PG 2 |
| WGK Germany | 3 |
| RTECS | LV2500000 |
| F | 1-8-10 |
| HazardClass | 6.1(a) |
| PackingGroup | II |
| HS Code | 29189090 |
| Storage Class | 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials |
| Hazard Classifications | Acute Tox. 3 Dermal Acute Tox. 3 Inhalation Acute Tox. 3 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3 |
| Hazardous Substances Data | 518-28-5(Hazardous Substances Data) |
| Toxicity | LD50 in rats (mg/kg): 8.7 i.v.; 15 i.p. (Phillips) |
| Description | Podophyllotoxin (2,3-butyl-4-aromatic naphthene) is isolated from guijiu(Podophyllum) . There are two species as the main source of podophyllotoxin, Podophyllum hexandrum Royle and Podophyllum peltatum . Although podophyllotoxin has significant antitumor and antiviral activities, it showed several toxicity and side effects. Podophyllotoxin derivatives, etoposide (VP-16-213), Etopophos, amino sugar etoposide (NK6l1), and teniposide (VM26), have been developed as anticancer drugs. They are used to treat small cell lung cancer, testicular cancer, acute leukemia, malignant lymphoma, etc. But podophyllotoxin derivatives are not free of toxicity. Besides the narrowing of the anticancer spectrum and low water solubility, these drugs could induce severe myelosuppression, gastrointestinal side effects, etc. Although the synthetic and biosynthetic pathways of podophyllotoxin have been elucidated, it is still the most effective, economic, and fast way to extract podophyllotoxin from the plant. |
| Chemical Properties | off-white fine crystalline powder |
| Physical properties | Appearance: white needle crystal powder. Solubility: freely soluble in chloroform, acetone, ethyl acetate, and benzene; soluble in ethanol and ethyl ether; and insoluble in water. Melting point: after drying the melting point is 183–184°C. Specific optical rotation: 132.7°C (chloroform). |
| History | Podophyllotoxin was first found in the Podophyllum peltatum L.?The first time to isolate podophyllotoxin from podophyllin was in 1880. In 1942, it was found that venereal warts could be effectively treated by application of podophyllin.Subsequently, podophyllotoxin was reported to inhibit the growth of the tumor through the inhibition of the microtubule formation. The chemical structure of podophyllotoxin was elucidated in 1951. In the 1960s, two main podophyllotoxin derivatives were synthesized, etoposide and teniposide (VM-26) . In 1983, etoposide was approved by FDA.?Etoposide and teniposide are used in frontline cancer therapy against various cancer types, such as small cell lung cancer, testicular cancer, etc. In 1996, etoposide phosphate analog (Etopophos) was launched in America. Etopophos is the prodrug of etoposide and can be rapidly absorbed and completely converted to the parent compound in?vivo. In 1990, WHO recommended 0.5% podophyllotoxin as the first-line drug for the treatment of condyloma acuminatum. Podophyllotoxin creams and gels are nowadays widely used in clinical practice. |
| Uses | Skin treatment for genital warts caused by some types of HPVs. |
| Uses | antineoplastic, inhibits microtubule assembly, and human DNA topoisomerase II; antimitotic agent |
| Uses | Podophyllotoxin is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species. It binds to topoisomerase II during the late S and early G2 stage, blocking tubulin polymerization and, thus, inhibiting mitosis. In addition to being used as a cathartic, purgative, antiviral agent, vesicant, and antihelminthic, podophyllotoxin is the starting material for the semi-synthesis of the anti-cancer drugs etoposide , teniposide , and etopophos. |
| Definition | ChEBI: An organic heterotetracyclic compound that has a furonaphthodioxole skeleton bearing a 3,4,5-trimethoxyphenyl substituent. It is found in the roots and rhizomes of Podophyllum species and is used for the topical treatment of genital warts. |
| Indications | Podophyllotoxin (Podofilox) is available alone and asthe main cytotoxic ingredient in podophyllin (25%podophyllum resin), a mixture of toxic chemicals derivedfrom May apple plants. The active ingredients inhibitcell mitosis. The drugs are used to treat condylomataacuminata. The most common toxic effects areskin irritation and less commonly, ulceration. Systemic absorption of podophyllin can occur (especially if appliedto large, inflamed areas or mucosal surfaces), withgastrointestinal, hematological, renal, and hepatotoxiceffects. In addition, seizures and peripheral neuropathyhave been reported. |
| Brand name | Condylox (Oclassen). |
| Biochem/physiol Actions | Inhibits microtubule assembly; antineoplastic. |
| Pharmacology | Antineoplastic and antiviral activities are the most pronounced pharmacological.effects of podophyllotoxin . Podophyllotoxin shows a significant inhibitory effect on the division and proliferation of epithelial cells infected by human papillomavirus (HPV), disrupts the cell cytoskeleton, and induces the necrosis and shedding of warts. It was shown that the antitumor effect of podophyllotoxin is associated with the inhibition of microtubule assembly and the induction of apoptosis. However, the antitumor effect of podophyllotoxin analogs, such as etoposide, teniposide, and Etopophos, is related to disparate mechanisms including the inhibition of DNA topoisomerase II activity and the formation of stable nucleic acid-drugenzyme complex, which induce DNA double-strand or single-strand break and eventually lead to cell death . It was also found that podophyllotoxin derivatives have immunosuppressive and anti-inflammatory effects. |
| Clinical Use | Podophyllotoxin is a useful agent for the treatment of condyloma acuminatum . Podophyllotoxin and its derivatives are also widely used in the treatment of cancer, such as lymphomas and lung carcinoma. Because of the several toxicity of podophyllotoxin, for example, the irritation of skin and mucous membranes, combination therapies are used to treat condyloma acuminatum or cancer. |
| Anticancer Research | Podophyllotoxin (PTOX) is an aryl-tetralin lignan and has been originallyisolated from Podophyllum peltatum L. (American podophyllum or Mayapple;family Podophyllaceae). Later, it is also isolated from several species like P.hexandrum Royle (Indian podophyllum) and P. pleianthum (Taiwanese podophyllum).PTOX has also been reported in other plants such as Linum spp., Callitrisspp., Juniperus spp., Thuja spp., Hyptis spp., Thymus spp., Teucrium spp., Nepetaspp., Dysosma spp., Diphylleia spp., and Jeffersoniana spp. (Ionkova 2007;Yousefzadi et al. 2010). PTOX shows strong cytotoxic activity against various cancercell lines. However, PTOX is too toxic for the treatment of neoplastic diseasesin humans; it is used as a precursor for chemical synthesis of semisynthetic antineoplasticdrugs, etoposide, Etopophos, and teniposide , which are successfullyused as antitumor agents (Holthuis 1988; Cragg and Newman 2005).Podophyllotoxin derivatives are used in the treatment of lymphomas, acute leukemia,and testicular, lung, ovarian, bladder, and brain cancer (Srivastava et al. 2005).Podophyllum spp. are the major source of PTOX, and their availability is limited innature, and some species are categorized as endangered. Moreover, the chemicalsynthesis of podophyllotoxin is an expensive process; therefore, biotechnologicalproduction of podophyllotoxin using plant cell and tissue cultures has been preferredby various research groups (Farkya et al. 2004). |
| Anticancer Research | Podophyllotoxin istoxic for humancells and is aprecursor ofsemisyntheticantineoplastic drugs(e.g., etoposide,etopophos, andteniposide). |
| Purification Methods | The toxin recrystallises form *C6H6 (with 0.5C6H6), EtOH/*C6H6, aqueous EtOH (with 1-1.5H2O, m 114-115o) and CH2Cl2/pentane. When dried at 100o/10mm it has m 183-184o. [UV: Stoll et al. Helv Chim Acta 37 1747 1954, IR: Schecler et al. J Org Chem 21 288 1956.] It is an inhibitor of microtubule assembly [Prasad et al. Biochemistry 25 739 1986]. [Beilstein 19/10 V 666.] |
Podophyllotoxin Preparation Products And Raw materials
