Vinblastine suppresses cell growth during metaphase, affects amino acid metabolism, in particular at the level of including glutamine acid into the citric acid cycle and preventing it from transformation into urea, and it also inhibits protein and nucleic acid synthesis.

Vinblastine is used for severe lymphoblastic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, sarcoma, and other cancerous diseases. Synonyms of this drug are velban, eczal, and others.

Vincristine: Vincristine, [3aR-[3aa,4/,5/,5a/,9(3R*,5S*,7R*,9S*),10bR*,13aa]]methyl-4-(acetyloxy)-9-[5-ethyl-1,4,5,6,7,8,9,10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,

7-methanoazacycloundecino-[5,4-b]indol-9-yl]-3a-ethyl-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-formyl-1H-indolizino[8,1-cd]-carbazol-5-carboxylate (30.4.2), is also isolated from V. rosea [121-123]. There also are semisynthetic ways of making this drug [124-126].

The mechanism of action of vincristine and indications for use are the exact same as with vinblastine. Synonyms of this drug are leurocristine, oncovin, and others.

30.4.1 Epipodophyllotoxins

Etoposide and teniposide are synthetic derivatives of the extract of the American mandragora plant (May Apple). The mechanism of their action has not been completely explained; however, they act on the enzyme topoisomerase II, which disturbs the twisting of DNA. In addition, they inhibit DNA and RNA synthesis, as well as transport of nucleotides to cells. Cytotoxic action on normal cells is observed only in very high doses. These drugs exhibit significant activity in lymphomas, leukemia, Kaposi's sarcomas, and in testicular cancer.

Etoposide: Etoposide, [[5R-(5a,5a/i,8aa,9^)]-9-[4,6-0-ethylidene-/i-D-glucopyranosyl) oxy]-] 5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3',4': 6,7]-naphtho[2,3-d]-1,3-dioxol-6(5a#)-one (30.4.5), is made from 4'-desmethylepipodophyllotoxin (30.4.3), the phenolic group of which being previously protected by benzyl chloroformate, which makes 4'-carbobenzyloxy-4'-desmethylepipodophyllotoxin (30.4.3). Next, the hydroxyl group at position C9 is esterified with 4,6-0-ethylyden-2,3-di-0-acetyl-/i-D-glucopyranose in the presence of boron trifluoride to make the corresponding glucopyranoside 30.4.4. Removing the acetyl group in the glucopyranosyl part of the molecule using zinc acetate in sodium methoxide, and also removing the benzyloxycarbonyl protection by hydrogenation using a palladium on carbon catalyst gives the desired etoposide (30.4.5) [127,128].

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