Use as anticancer agents

Dervan PB, Poulin-Kerstien AT, Fechter EJ, Edelson BS (2005) Regulation of Gene Expression by Synthetic DNA-Binding Ligands. 253 1-31 Dias N, Vezin H, Lansiaux A, Badly C (2005) Topoisomerase Inhibitors of Marine Origin and Their Potential Use as Anticancer Agents. 253 89-108 DiMauro E, see Saladino R (2005) 259 29-68... 

Two TV-nitrosoureas, Bischloroethyl-nitrosourea (BCNU) and l-chloroethyl-3-cyclohexyl-1-nitrosourea (CCNU), have been used as anticancer agents in clinics but their mechanism and their toxicities have yet to be determined78. 

In recent years, however, some of the greatest emphasis has been placed on the search for anticancer and antiviral agents derived from natural products. Success in that area has not heen as great as that achieved in other helds. Since 1960, only seven plant-derived drugs have heen approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol , topotecan, and irinotecan—were discovered and approved much more recently. 

Shiragami, T., Y. Shobu, M. Morino and C. Yoshikumi. Polyphenols and extraction of the compounds from Camellia sinensis (1.) O. Kuntze for use as anticancer agent-resistance inhibitors. Patent-Japan Kokai Tokkyo Koho-07 330,599 1995 6 pp. 

Ba[Pt(CN)4] is used in the production of fluorescent X-ray screens.94 Dichlorodihydroxy-diamine- and dichlorodinitratodiamine-platinum(IV) complexes show weak fungicidal activity, but there appears to be no likelihood of them actually being used to this end.95 Other applications of platinum complexes involve their use as anticancer agents, as selective stains in biology, in catalysis, in metallurgy and in photography, described in the relevant chapters of this volume. 

The fused bicyclic /3-lactones salinosporamide A and omuralide are potent selective inhibitors of proteosome function. Unfortunately, they have short half-lives in serum otherwise, they might be interesting candidates for use as anticancer agents. The fused bicyclic /3-lactam 520, which has similar but not identical molecular architecture to salinosporamide A, shows proteosome inhibition in vitro and indefinite stability in neutral aqueous solution. It is thought that 520 acts by acylation of the hydroxyl group of threonine in a proteolytic /3-subunit of the proteosome <2005JA15386>. 

We have examined the effects of llavonoids and isoflavonoids on the P-gp-and MRP- mediated MDR mechanisms in both mouse lymphoma and human breast cancer cell lines. The interactions of the drug transporters P-gp or MRP with flavonoids or isoflavonoids might be worth their use as anticancer agents, such as a single administration or a combination cancer therapy with cytotoxic agents such as mitomycin C (MMC). Differences in the activities of the P-gp and the MRP-mediated efflux pump could be found in the presence of flavonoids and isoflavonoids. 

The alkaloid colchicine (FI) isolated from the medicinal plant Colchicum autumnale L. (Liliaceae family) still is used to treat gout and familial Mediterranean fever. FI and thiocolchicine (F2) (SCH3 rather than OCH3 at C-10), which is more stable and more potent but slightly more toxic, are mitotic inhibitors that inhibit polymerization of tubulin (69). Although they show antileukemic activity, they are too toxic to use as anticancer agents, which prompts the synthesis of new, less toxic analogs. 

Four compounds are currently under clinical investigation for their use as anticancer agents (Fimre 1). These are ecteinascidin 743 (1), from the tunicate Ecteinascidia turbinateaplidine (dehydrodidemnin B, 2) from the ascidian Aplidium albicans dolastatin 10 (3) from the sea hare Dolabella auratium and bryostatin 1 (4) from the bryozoan Bugula neritina The marine environment has also been the source of a number of anti-inflammatory compounds such as pseudopterosin E, (5). The pseudopterosins constitute the major active components in a popular line of skin care products. ... 

All the gold compounds used in therapy today (chrysotherapy) are Au(I) compounds (45-47) (10-14). Gold has an intriguing chemistry dominated hy relativistic effects (48) and it is interesting to consider the reasons why Au(III) complexes are not used as anticancer agents like those of Pt(II) are used. 

Ojima, I., Inoue, T., Slater, J. C., et al. (1999) Synthesis of enantiopure F-containing taxoids and their use as anticancer agents as well as probes for biomedical problems, in Asymmetric Fluoroorganic Chemistry Synthesis, Application, and Future Directions, ACS Symposium... 

From the perspective of the clinical laboratory, the measurement of cytoldnes in biological fluids may be useful for monitoring progression of some tumors and for therapeutic monitoring when they are used as anticancer agents. 

Pacific Northwest.) Encyclopedic references comment that the antibiotics doxorubicin, daunorubicin, bleomycin, mitomycin, and dactinomycin are all antineoplastic or anticancer agents, but are mostly too toxie for antibiotic use (and perhaps are too toxic to be used as anticancer agents, a ease again of adverse side effects). 

The taxanes originally were extracted from the bark of the Pacific Yew tree and have found widespread use as anticancer agents. The structurally related taxanes, docetaxel and pacUtaxel, bind to and stabilize polymerized microtubules. Cells that enter mitosis in the presence of paclitaxel attempt to assemble a spindle apparatus, however the inhibition of depolymerization renders this structure unable to properly position chromosomes at the metaphase plate. Therefore, although kinetochores bind to microtubules, there is insufficient tension to inactivate the SAC. Paclitaxel-treated cells become blocked in mitosis, and eventually die by the mechanisms just described. Currently, there... 

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