Anticancer agents bleomycin

Resistance to the peptide antibiotic/anticancer agent bleomycin can occur through the expression of the Blm family of proteins that sequester the antibiotic. Bleomycin includes... 

Anticancer agents, 36 32-37, 45 253 bleomycin, 45 253-254 Antiferromagnetism, 21 260 coupling, in dinuclear system, 32 73... 

Hecht SM. Bleomycin group antitumor agents. In Anticancer Agents from Natural Products. Cragg GM, Kingston DGI, Newman DJ, eds. 2005. Taylor and Francis, Boca Raton, FL. pp. 357-381. 

Microbial sources have been a very rich source for cancer chemotherapeutic agents. Of particular note is the Strep-tomyces spp., which has been responsible for the production of many approved anticancer agents that are in clinical practice. These agents are represented by highly diverse structural classes exemplified by the anthracycline family (e.g., doxom-bicin, 73) (72-74), actinomycin family (e.g., dactinomycin, 74), glycopeptides family (e.g., bleomycins A2 and B2, 75 and 76) (75), and mitomycin family (e.g., mitomycin C, 77) (72, 76). All these compounds specifically interact with DNA for then-mode of action. 

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). 

A superb example of this approach is the total synthesis of bleomycin A2 (252) reported by Hecht. Bleomycin was isolated by Umezawa and co-workers Q nd shown to be a potent anticancer agent.l69 While determining the structure, it was shown that hydrolyses and other chemical manipulations of 252 gave nine identifiable fragments (a) aminopropyldimethyl sulfonium (253) (b) 2-aminoethyl-2, 4-bithiazole-4 -carboxylic acid (254) (c) L-threonine (255) (d) (2f ,3S,4R)-4-amino-3-hydroxy-2-methylpentanoic acid (256) (e) L-eryr/zro-(3-hydroxyhistidine (258) (f) (3-amino-P-(4-amino-6-carboxy-5-methylpyrimidin-2-yl)propionic acid (259) (g) a rearrangement product, L- 3-aminoalanine (257) (h) gulose (260) and, (j) carbamoyl mannose (261). 

Using electrochemistry, uv-visible absorption, esr, and C nmr spectroscopy, and with the help of three new bleomycin analogues, the Fe(II) and Fe(III) binding sites of the antitumor antibiotic bleomycin have been located. The drug appears to utilize the amine-pyrimidine-imidazole region for iron binding. The physical properties of the metal complexes and how those properties relate to the proposed mechanism of action of the anticancer agent is also discussed. 

V. Nakamoto. M. Hashida, S. Muranishi, and H. Sezaki. Studies on pharmaceutical modiheation of anticancer agents. II. Enhanced delivery of bleomycin into lymph by emulsions and drying emulsions. Chem. Pharm. Bull., 23 3125-3131. 1975. D. H. Napper. Polymer Stabilization of Colloidal Dispersion.s. London. Academic Press, 1983. 

Shimada et al, [29] reported a new drug delivery system using small siliea particles that can adsorb bleomycin and are easily transferred to the lymphatics to deliver a large dose of anticancer agents to the regional lymph nodes. As shown in Table 3, transplanted tumors had increased in size at the time of sacrifice in the... 

Bleomycin and cyclosporine are the two economically most important streptomycete peptide antibiotics used as antitumor agents and immunomodulators, although dactinomycin is important medically for several tumors (see Chemotherapeutics, anticancer Immunotherapeutic agents). 

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