Podophyllotoxin CAS 518-28-5

Podophyllotoxin works by inhibiting tubulin and preventing vascular bundles from gathering to form mitotic spindle. It can effectively inhibit herpes virus and mitosis in the middle period of cells, and is used for toxic sexually transmitted diseases.
It can be used to treat condyloma acuminatum in male and female genitals and perianal parts, and can inhibit the division and proliferation of epithelial cells with verrucous proliferation caused by human papillomavirus (HPV) infection, so as to make them necrosis and fall off, thus playing a role in treating condyloma acuminatum.
Inhibit that assembly of microtubule; Anti-tumor
Clinically, Podophyllotoxin is used for acute monocytic and acute myelomonocytic leukemia, acute myeloid leukemia, chronic eosinophilic leukemia, small cell lung cancer, non-Hodgkin's lymphoma, testicular cancer and so on.

King and Sullivan found that its mechanism of inhibiting cell growth is the same as colchicine at the molecular level, by preventing the formation of spindle, thus blocking the division of cells during metaphase of mitosis and chromosome condensation. Later, it was found that at the subcellular level, Podophyllotoxin acted by inhibiting tubulin to prevent vascular bundles from gathering to form mitotic spindles. However, Etoposide and Teniposide do not affect the aggregation of vascular bundles even at high concentrations, which is just the opposite of the mechanism of this product.
Loike and others believe that the large glucoside molecules in Etoposide and Teniposide molecules affect their inhibitory activity on vascular bundles, and they inhibit cell proliferation through other mechanisms. Therefore, Podophyllotoxin is speculated that both of them can inhibit cell proliferation in the late or early stage of mitosis, and single-stranded DNA that is broken by forming a complex with drugs can be detected in human cervical cancer cells. Further in vitro experiments showed that VP-16 only interacted with DNA at a certain position to induce the breakage of single-stranded DNA.

Through the above experiments, Podophyllotoxin is confirmed that a nuclease is playing a role in drug-induced DNA unwinding and breakage. Other studies have also shown that VP-16 can form covalent complexes with a protease, leading to DNA unwinding and breakage. Based on the fact that topoisomerase can catalyze DNA unwinding, it is speculated that it is related to DNA breakage, and it is found that some anti-tumor drugs can inhibit the activity of TOPII. Because DNA topoisomerase (TopII) is a biological enzyme widely existing in organisms, it can adjust the dynamic changes of the spatial structure of nucleic acids and control the physiological functions of nucleic acids. Its function involves all aspects of nucleic acid metabolism, including DNA replication and transcription, chromosome separation, chromosome structure concentration and gene expression.
Topoisomerase mainly includes two types: TOPI and TOPII, which have some identical and overlapping functions, thus achieving complementary functions, but also have some important differences. TOPI is a gap that breaks a single strand on a DNA double strand, so that another single strand can pass through the gap. Therefore, TOPI can change the situation that DNA is super-spiral or under-spiral.

Sinha put forward a mechanism of free radical action of VP-16 through related research. Later, a large number of experimental results also supported this view, and Podophyllotoxin was believed that the dimethoxyphenol ring (E ring) in drug metabolites activated by metabolism formed chemical complexes with DNA to inactivate DNA. It was also found that 3',4'- catechol derivatives of Etoposide could be formed in the presence of cytochrome P-450, and could be further oxidized to 3', 4'- catechol derivatives in the presence of oxygen or peroxide. The derivatives of catechol and catechol can strongly bond with calf thymus DNA by forming free radicals or in the form of quinones, which is considered to be the active mechanism. Therefore, understanding the mechanism of action of this product and its derivatives can better guide the selection and synthesis of new drugs to improve activity and reduce toxic and side effects.