Antineoplastic compounds

Electrolysis as a means of removing contaminants from water works on the premise that the electrolyzed products generate h5q)ochlorite (Morita et al., 2000 Nakajima et al., 2004 Kiura et al., 2002) in the presence of a low concentration of sodium chloride. Hirose et al. (2005) electrolyzed several antineoplastics, eliminating their biological activity and toxicity. The actual electrolysis was done with a cocktail of antineoplastic compounds in a 0.07 M NaCl solution using two platinum-irridium... 

Bertram, B. and Wiessler, M. (2000) Biodegradability of antineoplastic compounds in screening tests influence of glucosidation and of stereochemistry. Chemosphere, 40 (7), 767-773. 

In conclusion, a novel type of antineoplastic compounds, substituted 6-phenylpurine ribonucleosides, has been discovered. In our view, the cytostatic activity of this class of compounds cannot be deduced from any known cytostatic nucleoside or purine derivatives, and therefore, it might be considered a new structural lead in the search for antitumor compounds. 

Guaianolides (C5 C7 C40L) include many cytotoxic and antineoplastic compounds. Various guaianolides are bitter tasting and insect antifeedants. Zaluzanin inhibits bacterial lipopolysaccharide-induced NFKB-mediated expression of iNOS by immune cells and cynaropicrin inhibits similar induction of TNF-a expression through formation of a covalent protein adduct. Costunolide, 7-hydroxycostunolide and 3,4-epoxydehydroleucodin act in a similar manner to inhibit NFkB binding to DNA. 

There appears to be a fundamental law of heterocyclic chemistry that the greater the ratio of heteroatoms to carbon atoms the more likely the final compound in the synthetic scheme is to be formed by ring closure. When the references for this chapter were finally assembled, more than 80% dealt only with synthesis by cyclization methods. Much of this work has been stimulated by the discovery of potent antibiotic and antineoplastic compounds (Section 4.05.5). 

Aminopyrazoles (292) carrying ribosyl groups are used to prepare potential antineoplastic compounds (Scheme 88). The aminopyrazolotriazine (293) is readily hydrolyzed (see Section 4.05.3.3) to (294). After deprotection of the sugar residue, both derivatives showed activity against leukemic cells (B-78MI40500). 

The seminal discoveries of taxol (tubulin-interactive) and camptothecin (topo I-interactive) by Wall and Wani (14—16) represent how natural products have influenced the additional development of natural product-derived and synthetic entities. The following discussion of the discovery and development of current important antineoplastic compounds will be organized by plant species. 

Dolastatin 10 (1) appears to be one of the most potent antineoplastic compounds known to date. The isolation of a closely related analogue from a cultivable source is significant, as this potentially allows study of its biosynthesis. 

Many other polymers with antineoplastic properties have been prepared. For the most part, these polymers contain a known antineoplastic compound attached to the polymer chain as a pendant group. The earliest examples of this type seem to be the aziridine alkylating group containing polymers (XIX) (52), and (XX) (53), and (XXI) (54) which contains the cytostatic agent sarcolysin. 

Combretastatins. Antineoplastic compounds from the South African tree Combretum caffrum (Com-bretaceae) which has many uses in traditional medicine. C. caffrum contains stilbenes, bibenzyls, phenanthrenes, and diaryl ethers such as the cytotoxic C.D2 which are grouped together under the name C. 

Glatt, H., Eich, E., Pertz, H., Beckei C. and Oesch, F. (1987) Mutagenicity experiments on agroclavines, new natural antineoplastic compounds. Cancer Res., 47, 1811-1814. 

A new synthesis of the antineoplastic compound, podophyllotoxin (57), has been reported. It scores over previous approaches in that the problem of epimerization of the C-2 carboxyl group is avoided by the use of the acetonide protecting group in the key intermediate (56). This controlling element forces (56) into a conformation with axial phenyl and equatorial ester, thus removing the usual driving force for epimerization at C-2. 

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