Of epipodophyllotoxin

For patients with myelodysplastic syndrome or AML as a secondary neoplasm, there are a number of key features characteristic of the leukemia. Alkylator-related secondary leukemias after Hodgkin s disease usually have a myelodysplastic prodrome and a monosomy 5 or monosomy 7. Secondary ANLL with the use of epipodophyllotoxin (etoposide) demonstrates mainly M4 or M5 morphology and exhibits translocations within the MLL gene with 1 lq23 chromosomal alterations.8... 

Fig. 4 Synthesis of epipodophyllotoxin through a Diels-Alder reaction (taken from [39] by permission from Kluwer)...

Xiao Z, Xiao YD, Feng J, Golbraikh A, Tropsha A, Lee KH. Modeling of epipodophyllotoxin derivatives using variable selection k nearest neighbor QSAR method. J. Med. Chem. 2002 45 2294-2309. 

Leukaemias and Haematosarcomas. Clinical screening of epipodophyllotoxin VM26 in malignantlymphomasandsolidtumours. Br Med J. 1972 2 744 748... 

Antitumour Agents. 213. Modeling of Epipodophyllotoxin Derivatives Using Variable Selection k Nearest Neighbor QSAR Method. 

Podophyllotoxin is used externally to treat condylomata acuminata (soft warts). Etoposide is a semi-synthetic derivative of epipodophyllotoxin glycoside, currently being used for the treatment of cancer. 

Engelhardt U, Sarkar A, Linker T. Efficient enantioselective total synthesis of ( ) epipodophyllotoxin. Angew. Chem. Int. Ed. Engl. 2003 42(22) 2487-2489. 

Serretta V, Ingargiola GB, Pavone-Macaluso M. The role of epipodophyllotoxin derivatives in bladder cancer. Semin. Oncol 1992 19 81 4. 

Hyaluronidase is the antidote of choice for vinca alkaloid and high-concentration epipodophyllotoxin extravasations. Hyaluronidase breaks down hyaluronic acid, which functions as tissue cement. This promotes absorption of the extravasated drug away from the local site. Hyaluronidase also may be used for paclitaxel extravasations, but there are conflicting reports regarding its efficacy.39 Hyaluronidase should not be used with anthracycline extravasations because enhancement of local spread may occur. 

The vinca alkaloids vinblastine and vincristine are capable of producing the MDR phenotype in a wide variety of cell types. Furthermore, cells that are made resistant to antitumor drugs such as doxorubicin, actinomy-cin D, or the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26) are often resistant to the effects of the bisindole alkaloids. The structural and mechanistic diversity of these compounds is even more striking against the backdrop of collateral resistance. 

Augmented drug extrusion increased synthesis of the P-glycoprotein that extrudes drugs from the cell (e.g., anthracyclines, vinca alkaloids, epipodophyllotoxins, and paclitaxel) is re-ponsible for multi-drug resistance (mdr-1 gene amplification). 

Teniposide is used for the same indications as etoposide however, it is 5-10 times more potent than etoposide. Synonyms of this drug are epipodophyllotoxin, vumon, and others. 

Multiple-drug chemotherapy regimens consisting of various combinations of BCNU, hydroxyurea, procarbazine, and/or VM-26 (epipodophyllotoxin) showed no significant survival advantage over BCNU alone (BTCG 8001). 

Stewart DJ, Grahovac Z, Benoit B, et al. Intracarotid chemotherapy with a combination of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU), cis-diaminedichloroplatinum (cisplatin), and 4 -0-demethyl-l-0-(4,6-0-2-thenylidene-beta-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the treatmentof primary and metastatic brain tumors. Neurosurgery 1984 15(6) 828-833. 

Tafluposide (F 11782) is an epotoside (epipodophyllotoxin) derivative (cf. Chapter 4) where the two hydroxyls of the glycosidic moiety are acylated with pentafluorophenoxyacetic acid (Figure 8.7). It has been demonstrated that tafluposide does not act as a prodrug of epotoside, but it has a unique mechanism of interaction with both topoisomerases I and... 

Covalently linked conjugates, (II), consisting of a topoisomerase I inhibitor such as a camptothecin group and a topoisomerase II inhibitor such as epipodophyllotoxin, were prepared by Lee (1) and used in treating small cell lung cancer. 

The conjugate of two molecules with different functions or mechanisms of action often displayed dual functions or enhanced activities. Based on this rationale, Shi et al. prepared five taxoid-epipodophyllotoxin dimers. All dimers showed... 

Shi Q, Wang HK, Bastow KF, Tachibana Y, Chen K, Lee FY, Lee KH. Anhtumor agents 210. Synthesis and evaluation of taxoid-epipodophyllotoxin conjugates as novel cytotoxic agents. Bioorg. Med. Chem. 2001 9 2999-3004. 

Bastow KF, Wang HK, Cheng YC, Lee KH. Antitumor agents 59. 173. Synthesis and evaluation of camptothecin-4P-amino-4 -0-demethyl epipodophyllotoxin conjugates as inhibitors of mammalian DNA topoisomerases and as cytotoxic agents. Bioorg. 60. Med. Chem. 1997 5 1481-1488. 

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