Podophyllotoxin
podofilox · PODOPHYLLIC ACID LACTONE · (-)-PODOPHYLLOTOXIN · condylox · Condyline · β-Arteether · (5R,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one · nsc24818
식별자 및 물리적 특성
| CAS No. | 477-47-4 |
|---|---|
| 분자식 | C22H22O8 |
| 평균 분자량 | 414.4 g/mol |
| 단동위원소 질량 | 414.13146766 g/mol |
| SMILES | COc1cc([C@@H]2c3cc4c(cc3[C@H](O)[C@H]3COC(=O)[C@H]23)OCO4)cc(OC)c1OC |
| InChIKey | YJGVMLPVUAXIQN-XVVDYKMHSA-N |
| PubChem CID | 10607 |
| ChEMBL | CHEMBL61 |
| ChEBI | CHEBI:50305 |
| EC No. | 208-250-4 |
| DTXSID | DTXSID3045645 |
화학 및 물리적 성질
| XLogP | 2 |
|---|---|
| 극성 표면적 | 92.7 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 8 |
| 회전 가능 결합 수 | 4 |
| 무거운 원자 수 | 30 |
| 형식 전하 | 0 |
| 복잡도 | 629 |
| LogP(분배 계수) | 1.5log Kow = 2.01 |
| Color/Form | Solvated crystals |
| 용해도 | 100Insoluble in ethyl ether, ligroinslightly soluble in watersoluble in acetone, benzenevery soluble in ethanol, chloroform.In water, 150 mg/L at 25 °C /Estimated/1.14e-01 g/LDMSO:15.0(Max Conc. mg/mL)36.2(Max Conc. mM) |
| 녹는점 | 228114-118 °C183 °CMP: 114-118 °C (effervescence)228 °C183-184 °C (lit.) |
| 증기압 | 8.3X10-15 mm Hg at 25 °C /Estimated/ |
| Optical Rotation | Hygroscopic amorphos white flakes, mp = 152-154 °C. Specific optical rotation = -76.4 deg (c=0.576 in methanol)specific optical rotation = -117.0 deg (c=0.668 in pyridine) /Podophyllotoxin-beta-D-glucoside/Specific optical rotation = -132.7 deg @ 20 °C/D, chloroform, 2% |
| 헨리 상수 | Henry's Law constant = 3.8X10-18 atm-cu m/mol at 25 °C /Estimated/ |
| Physical Description | Light-brown to greenish-yellow powderCommercial resin preparations contain 5-25% podophyllum. [INCHEM]Solid |
| Collision Cross Section | 198.37 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]189.74 Ų [M+H]+ [CCS Type: TW199.47 Ų [M+K]+ [CCS Type: TW187.85 Ų [M+H-H2O]+ [CCS Type: TW190.1 Ų [M+H-H2O]+ [CCS Type: TW189.6 Ų [M+H]+ [CCS Type: TW |
| Other Experimental Properties | Several polymorphic modifications. After drying up: mp = 183.3-184.0 °C. Specific optical rotation = -132.7 deg @ 20 °C/D (chloroform). Solubility in water at 23 °C = 12- mg/L. Soluble in alcohol, chloroform, acetone, warm benzene, glacial acetic acid.MW: 414.40. Crystals from acetone. MP = 214 °C. Higher-melting modification from abs ethanol, mp 228 °C. Specific optical rotation = +9.4 deg (c=0.7 in chloroform). Solubility in water at 25 °C approx 100 mg/L. Fairly soluble in chloroform, hot ethanol, acetic acid, acetone, dilute causticless soluble in benzene ether, carbon tetrachloride, propylene glycol. /Picropodophyllin/Hydroxyl radical reaction rate constant = 2.2X10-10 cu cm/molecule-sec at 25 °C /Estimated/ |
| 끓는 점 | 453.31°C (rough estimate) |
| 밀도 | 1.2649 (rough estimate) |
| 굴절률 | 1.4480 (estimate) |
| 저장 조건 | 2-8°C |
| pKa(산도 계수) | 13.26±0.40(Predicted) |
| 물리적 상태 | 가루 |
| 색상 | 흰색에서 황백색까지 |
| Merck | 13,7628 |
| BRN | 99163 |
| 안정성 | 흡습성이 매우 높음 |
| InChIKey | YJGVMLPVUAXIQN-XVVDYKMHSA-N |
| SMILES | COc1cc(cc(OC)c1OC)[C@H]2C3C(COC3=O)[C@@H](O)c4cc5OCOc5cc24 |
| LogP(분배 계수) | 2.010 |
화학적 성질
off-white fine crystalline powder
안전 및 규제
| GHS 분류 | This chemical does not meet GHS hazard criteria for 2.2% (1 of 46) of reports.DangerH301 (93.5%): Toxic if swallowed [Danger Acute toxicity, oral]H310 (95.7%): Fatal in contact with skin [Danger Acute toxicity, dermal]H315 (97.8%): Causes skin irritation [Warning Skin corrosion/irritation]H319 (97.8%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]H335 (95.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposureRespiratory tract irritation]P261, P262, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 46 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 1 of 46 reports by companies.There are 7 notifications provided by 45 of 46 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| 규제 정보 | Chemical: 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-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]- |
| 기타 안전 정보 | IMAP assessments - 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-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-: Environment tier I assessmentIMAP assessments - 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-(5.alpha.,5a.beta.,8a.alpha.,9.alpha.)]-: Human health tier I assessment |
| 화재 가능성 | Podofilox topical gel is flammable and should be kept away from open flames. |
| 유해성 요약 | The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [ChemIDplus] |
용도
개요
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.
역사
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 invivo. 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.
용도
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.