Iron bleomycin natural

The natural product bleomycin mediates strand scission in the presence of iron and oxygen by a related mechanism (6, 12, 14) however, no diffusible intermediate is generated. Electrochemical and related studies showed that the mechanism of iron bleomycin (Fe-BLM) involves first reduction of Fe(III)-BLM, reaction of Fe(II)-BLM with 02, and reduction of the Fe(II)-BLM-02 adduct to activated Fe-BLM (15). 

Iron bleomycin (FeBLM) is a natural product with anticancer activity that is thought to arise from nucleic acid damage and has been termed... 

One family of antitumorigenic compounds used in practice are the bleomycins, natural products that contain iron isolated from Streptomyces cultures. Bleomycin sulfate is used in combination chemotherapy for treatment of head and neck cancer. The mechanism of action of bleomycin is believed to include the binding of oxygen to form 02-Fe(II)-BLM. This complex can accept an electron to produce an active species, 02 -Fe(III)-BLM, which can cleave DNA and RNA, ultimately killing the cancer cell. 

Bleomycin is a naturally occurring fermentation product of Streptomyces verticillus. It is a basic glycoprotein, complexed with Cu++. It intercalates between DNA base pairs, and it also chelates iron, generating oxygen radicals which further damage the DNA. It is the only cell-cycle specific agent among the antibiotics as it causes accumulation of cells in the G2 phase of the cell cycle. 

Since H202 is easier to handle than 02, we will focus on the use of the former. Many metals can be used for this transformation [50]. Among them, iron compounds are of interest as mimics of naturally occurring non-heme catalysts such as methane monooxygenase (MMO) [51a] or the non-heme anti-tumor drug bleomycin [51b]. Epoxidation catalysts should meet several requirements in order to be suitable for this transformation [50]. Most importantly they must activate the oxidant without formation of radicals as this would lead to Fenton-type chemistry and catalyst decomposition. Instead, heterolytic cleavage of the 0—0 bond is desired. In some cases, alkene oxidation furnishes not only epoxides but also diols. The latter transformation will be the topic of the following section. 

The antitumour action of the natural antibiotic bleomycin is thought to involve the aerobic degradation of DNA by the Fe2+-bleomycin complex. In order to probe the mechanism of antitumour action of bleomycin, the 4-ethylamido[5,(2 -thienyl)-2-thiophene] imidazole iron(II) complex was synthesized [129]. It was studied in non-aqueous solution using cyclic voltammetry and showed antitumour activity in vitro, its action causing cleavage of the double helical DNA. 

There are now more than forty drugs approved for the treatment of human cancer in the United States. Considering the thousands of compounds that have been tested as candidate antitumor agents, this is a highly select group. Among them are two drugs that require a metal ion as part of their structures. One is the simple metal complex cis-diamminedichloroplatinum(ii). The other, bleomycin, is a natural product that must form an iron complex to display cytotoxicity. In addition, two anthracycline natural products, doxorubicin or adriamycin, and daunomycin, may also function as iron complexes or utilize cellular iron in an indirect way in their mechanisms of action. 

Bleomycin is a natural product isolated from Streptomyces verticillus. It normally Is chelated with Cu, which must be removed via catalytic reduction before marketing. This increases the cost of the drug, but it frees up the critical bleomycin functional groups for chelation with intracellular ferrous iron. 

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