What Is Podophyllotoxin?

Podophyllotoxin is a lignan antitumor component extracted from the roots and stems of the podophyllotus plant of the genus Berberidaceae, also known as chicken podophyllotoxin. It is a white crystalline powder, odorless and hygroscopic. Chinese ghosts are mainly distributed in Gansu Province and other places in China. Podophyllotoxin extracted from Chinese podophyllotoxin (also known as chicken lichen) can be made into creams and tinctures. Podophyllotoxin can effectively inhibit herpes virus, inhibit mitosis in the middle period of cells, and is used for toxic diseases. ^[1]

CAS number: 518-28-5

MDL: No

EINECS: No

RTECS number: No

BRN: No

PubChem number: ^[1]

1. Properties: Strong yellow powder

2. Density (g / cm3, 25/4 ): Not determined

3. Relative vapor density (g / cm3, air = 1): not determined

4. Melting point (ºC): 117-119

5. Boiling point (ºC, atmospheric pressure): 303

6. Boiling point (ºC, 8kPa): Not determined

7. Refractive index: Not determined

8. Flash point (ºC): Not determined

9. Specific rotation (º): Not determined

10. Spontaneous ignition point or ignition temperature (ºC): Not determined

11. Vapor pressure (kPa, 25ºC): Not determined

12. Saturated vapor pressure (kPa, 60ºC): Not determined

13. Combustion heat (KJ / mol): Not determined

14. Critical temperature (ºC): Not determined

15. Critical pressure (KPa): Not determined

16. Logarithm of oil-water (octanol / water) partition coefficient: not determined

17. Upper explosion limit (%, V / V): Not determined

18. Lower explosion limit (%, V / V): Not determined

19. Solubility: easily soluble in water ^[1]

No

This substance may be harmful to the environment. Special attention should be given to water bodies. ^[1]

No

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 1

3.Number of hydrogen bond acceptors: 8

4.Number of rotatable chemical bonds: 4

5.Number of tautomers: 2

6. Topological molecular polar surface area 92.7

7.Number of heavy atoms: 30

8.Surface charge: 0

9.Complexity: 629

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 4

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[1]

Use and store according to specifications without decomposition and avoid contact with oxides ^[1]

Store in a cool, dry, well-ventilated warehouse. Keep away from fire and heat sources. Protect from direct sunlight. Packaging is sealed. It should be stored separately from acids and edible chemicals. The storage area should be equipped with suitable materials to contain spills. ^[1]

It was extracted from the rhizomes of the Berberidaceae plant Chinese mountain lotus leaf (Diphylleia sinensishi Li). ^[1]

It is mainly used for condyloma acuminatum and can also be used for other viral warts.

Inhibits microtubule assembly; anti-tumor. It is clinically used in acute mononuclear cell type and acute granulocyte monocyte type leukemia, acute myeloid leukemia, chronic eosinophilic leukemia, small cell lung cancer, non-Hodgkin's malignant lymphoma, testicular cancer, and the like. ^[3]

Dangerous Transport Code: No

Dangerous Goods Sign: Toxic

Safety identification: S45

Danger sign: R23 / 25 ^[1]

477-48-5 PPPone ~ 77% 518-28-5 Podophyllotoxin

Literature: Stadler, Daniel; Bach, Thorsten Angewandte Chemie-International Edition, 2008, vol. 47, # 39 p. 7557-7559

Structural formula 1256-91-3 ~ 85% 518-28-5 Podophyllotoxin

Literature: Bush; Jones Journal of the Chemical Society-Series Chemical Communications, 1993, # 15 p. 1200-1201

(-)-4-O- (tert-butyldimethylsilyl) podophyllotoxin 112711-16-7 ~ 76% 518-28-5 Podophyllotoxin

Literature: Andrews, Robert C .; Teague, Simon J .; Meyers, AI Journal of the American Chemical Society, 1988, vol. 110, # 23 p. 7854-7858

Podophyllotoxin against

1. Protect the surrounding area with petroleum jelly to avoid contamination of the medicinal solution, or use talcum powder to spray the treatment area immediately after application.

2. Dip a toothpick or glass rod into the medicine solution, and then drop it once, and then dry it to make the medicine solution damaged. Keep it for 1 to 6 hours, then wash it with soap and water. If the medicine solution contains benzoin, use alcohol cotton balls Wipe clean and wash hands immediately after application. The interval between the two treatments is at least 7 days, and the treatment can be performed 4 times. If it still fails, other therapies need to be replaced. Usually applied concentration is 25%, large area damage (> 10 ~ 20cm) applied concentration of 5% ~ 10%.

3. For condyloma acuminatum, use a 10% to 25% solution for 1 to 6 hours, once a week for a total of 4 times.

4. For multiple superficial epithelioma or anterior epithelioma keratosis, apply 25% solution once a day for several consecutive days.

5. For juvenile laryngeal papilloma, external use is diluted with an equal amount of 95% alcohol to 12.5%, once a day. When the damage is reduced, the interval can be applied. ^[2]

   Topical application and ingestion can cause severe systemic toxic effects, which are usually reversible but also lethal. Oral 300mg can be lethal. Large-area external coating, excessive coating, long-term application can cause serious toxic reactions. This product can be applied to areas that are crunchy, bleeding, or recently biopsy of warts or to normal skin or mucous membranes around diseased areas, which can increase the risk of systemic poisoning. External use can cause renal failure and liver poisoning (serum lactate dehydrogenase,

   King and Sullivan found that the mechanism by which podophyllotoxin inhibits cell growth at the molecular level is the same as that of colchicine, by blocking the formation of spindles, thereby blocking cell division during mitosis and chromosomal condensation. It was later discovered that at the subcellular level, podophyllotoxin works by inhibiting tubulin to prevent vascular bundles from forming mitotic spindles. However, Etoposide and Teniposide do not affect the aggregation of vascular bundles even at high concentrations, which is the exact opposite of the mechanism of action of podophyllotoxin. Loike et al. Believe that the large glucoside molecules in Etoposide and Teniposide molecules affect its inhibitory activity on vascular bundles, and they inhibit cell proliferation through other mechanisms of action. Therefore, it is speculated that both can inhibit cell proliferation in the late or early stages of cell mitosis, and detect single-stranded DNA that is complexed with drugs and broken in human cervical cancer passage cells. Further in vitro experimental studies found that VP-16 only interacts with DNA at a specific location to induce the breakage of single-stranded DNA. The above experiments confirmed that a nuclease is playing a role in drug-induced DNA unwinding and cleavage. Other studies have also shown that VP-16 can form covalent complexes with certain proteases, resulting in DNA unwinding and cleavage. Based on the role of topoisomerase in catalyzing DNA unwinding, it is speculated that it is related to DNA breakage, and some antitumor drugs have been found to inhibit the activity of TOPII. Because DNA topoisomerase (TopII) is a biological enzyme that is widely present in organisms, it can regulate the dynamic change of the spatial structure of nucleic acids and control the physiological functions of nucleic acids. Its role involves all aspects of nucleic acid metabolism, including DNA replication and transcription, chromosome isolation, chromosome structure enrichment, and gene expression. Topoisomerases mainly include two types: TOPI and TOPII, both of which have certain identical and intersecting functions, thus complementing each other's functions, but also having some important differences. TOPI is a gap that creates a single-strand break on the DNA double-strand, allowing another single-strand to pass through the gap. Therefore, TOPI can change the situation of DNA super-coil or under-helix. TOPII creates a double-strand break in the DNA backbone, allowing another double-strand to pass through the gap. In this process, ATP needs to provide energy. TOPII is also involved in the processes of DNA replication, transcription, recombination, and chromosome organization. It is an indispensable key enzyme for the survival of all eukaryotic cells. TOPII has become an important target for anti-tumor drugs. According to its mode of action, it can be roughly divided into two types: one is to inhibit the total catalytic activity of TOPII, which is called TOPII catalytic inhibitor; the other is to inhibit TOPII in a unique way. The catalytic function of TOPII is to capture the DNA fragmentation complexes of TOPII mediators and cause the accumulation of DNA double bond breaks to trigger cell death, which is called TOPII poison. Podophyllotoxin derivatives such as VP-16 belong to the latter, namely TOPII poison.

   Sinha proposed a mechanism of action of o-benzoquinone radical of VP-16 through related research. Later, a large number of experimental results also support this view, which is believed to play a role by inactivating DNA by forming a chemical complex with the dimethoxyphenol ring (E ring) in the drug-activated drug metabolite and DNA. The experiment also found that 3 ', 4'-catechol derivatives of Etoposide can be formed in the presence of cytochrome P-450, and can be further oxidized to 3', 4'-catechol in the presence of oxygen or peroxide. Quinone derivatives. Both catechol and phthaloquinone derivatives can be strongly bonded to calf thymus DNA by forming free radicals or in the form of quinones, which is considered to be the mechanism of their activity. Therefore, understanding the mechanism of action of podophyllum and its derivatives can better guide the selection of new drugs to increase activity and reduce toxic and side effects. ^[2]