Cancer antitumor agents

W. A. Renters, B. S. Iyengar, Cancer chemotherapeutic agents, va. Antitumor Antibiotics... 

The dicytodendrins A-E (Fig. 9) are one of the most recent 3,4-diarylpyrrole natural products to be reported [64], Their isolation by Fusetani and coworkers from a Japanese marine sponge was reported in 2003. These substances (144-148) have been shown to inhibit telomerase at a concentration of 50 pg/mL thereby making such compounds potentially useful as antitumor agents given that telomerase activity is found in 90% of cancer cells but... 

Synthetic a-carbolines have also attracted interest as antitumor agents. For example, Chen and coworkers [97] prepared a series of indolo[2,3-fr] quinoline derivatives, the most active of which was 154, which had a mean GI50 value against three cancer cell lines of 0.78 iM. This compound was prepared by methylation of 153 with dimethyl sulfate (Fig. 43), and was isolated in 12% yield, along with isomeric 155, which was isolated in 40% yield, but had significantly lower cytotoxicity. Precursor 153 itself was found to be inactive. 

Although N-methyl-N-nitrosourea can induce cancer in human beings, its derivatives were found to be potent antitumor agents. l,3-Bis(2-chloroethyl)-l-nitrosourea (BCNU), l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and l-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-l-nitrosourea (PCNU) l-(2-Choroethyl)-3-(4-methylcyclo-hexyl)-l-nitrosourea and l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea showed antitumor activity by alkylating with DNA [82-84]. N-Nitrosourea-based prodrugs designed to become activated by tumor-associated proteases were found to provide enhanced... 

Slichenmyer WJ, Rowinsky EK, Donehower RC, Kaufmann SH. The current status of camptothecin analogues as antitumor agents. J. Natl. Cancer Inst. 1993 Feb 17 85(4) 271-91. 

Hurley LH, Zewail-Foote, M (2001) The antitumor agent ecteinascidin 743 characterization of its covalent DNA adducts and chemical stability. Adv Exp Med Biol 500 289-299 Inche AG, La Thangue NB (2006) Chromatin control and cancer-drug discovery reaUzing the promise. 

The antitumor agent compound 593 A, was isolated from Streptomyces griseoluteus. This compound possesses the /3-chloramine function of the nitrogen mustards, a group of compounds whose derivatives have been incorporated into many synthetic drugs used in cancer chemotherapy. ... 

Matsumura, Y, and Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res., 1986, 46, 6387-6392. 

The most obvious difference between a normal cell and a cancerous one is that control of cell division has been lost in the latter. Since cell division requires synthesis of DNA, the synthesis, structure, and function of DNA have been frequent targets for discovery of antitumor agents. One of the problems with this approach is that some perfectly normal cells in the human body also turn over rapidly, including the cells in the bone marrow that eventually lead to the blood cells and the cells that line the gut. It is not surprising that the dose-limiting toxicity of many cancer drugs is damage to the bone marrow or the gut. 

Bentle MS, Reinicke KE, Dong Y, Bey EA, Boothman DA. (2007) Nonhomologous end joining is essential for cellular resistance to the novel antitumor agent, beta-lapachone. Cancer Res 67 6936-6945. 

The isolation of the antitumor agents vincaleukoblastine (1) and leuro-cristine (2) from Catharanthus roseus (L.) G. Don has proved to be one of the most important developments in both natural product chemistry and the clinical treatment of cancer during the 1960s to 1980s. More alkaloids (over 90) have been isolated from C. roseus than from any other plant, and because of the complexity of the alkaloid mixture this work has required the most advanced isolation and structure determination techniques. The exceptional interest in the broad spectrum of antitumor activity of these compounds has resulted in numerous achievements in the pharmaceutical, clinical pharmacologic, and therapeutical sciences. Simultaneously, strenuous efforts have been made in three areas of the natural product chemistry (i) elaboration of a practical semisynthesis of... 

The conjugation of deacetylvinblastine to a monoclonal antibody that recognizes a tumor-associated antigen results in an agent with substantial antitumor activity in mice with relatively little toxicity (la). Conjugates of this type are of obvious interest for future clinical trials as site-directed cancer chemotherapeutic agents. 

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