epipodophyllotoxin


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ep·i·po·do·phyl·lo·tox·in

(ep-i-pō'dō-fil-ō-toks'in),
Natural product that inhibits topoisomerase II.
[epi- + Podophyllum, genus name of botanical source, + toxin]
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--topoisomerase inhibitors that are inserted between the pairs of DNA bases disrupting the nucleic acids function or synthesis (topotecan, irinotecan and epipodophyllotoxin derivatives such as etoposide);
Currently used anticancer drugs such as taxol, camptothecin, epipodophyllotoxin, and vinblastine are derived from plant sources and there are several more plant derived anticancer compounds in clinical trials [5].
[3] Plant-derived compounds have also been an important source of several clinically useful anticancer agents, which include vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide derived from epipodophyllotoxin, and paclitaxel (taxol).
For example, piperonyl butoxide, isosafrole, kavalactones, podophyllotoxin, and epipodophyllotoxin are involved in the inhibition of CYP activity (Mathews et al.
Pouillart, "Two epipodophyllotoxin derivatives, VM 26 and VP 16213, in the treatment of leukemias, hematosarcomas, and lymphomas," Cancer, vol.
Several anticancer agents including Taxol, vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, and etoposide derived from epipodophyllotoxin are in clinical use all over the world.
On the other hand, the variant allele was observed to be a protective factor for treatment-related leukemia, whereas the wild-type allele for this polymorphism of CYP3A4 was associated with increased metabolism of epipodophyllotoxin, a chemotherapy agent, leading to leukemas with MLL gene translocations (6).
PEPEG, a new antineoplastic epipodophyllotoxin. Clin Pharmacol Ther 1975;18:221-6.
Several drugs currently used in chemotherapy were isolated from plant species.The best known are the Vinca alkaloids, vinblastine and vincristine, isolated from Catharanthus roseus, etoposide and teniposide, which are semi-synthetic derivatives of the natural product epipodophyllotoxin, Paclitaxel isolated from the bark of Taxus brevifolia, the semi-synthetic derivatives of camptothecin, irinotecan and topotecan, isolated from Cam ptotheca acuminata, among several others (Cragg et al.
O- demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4.