BLEOMYCINS

Definition

Bleomycins are a family of compounds produced by Streptomyces verticillis.

Enzyme inhibitor

This set of glycopeptide antibiotics and anticancer agents (Bleomycin A1: FW = 1415.55 g/mol; CAS 11056-06-7; R = –NH (CH2) 3-SOCH3); Bleomycin A2, R = –NH (CH2) 3-S+CH3); Bleomycin B1, R = –NH (CH2) 4- NCH (=NH) NH2); Bleomycin A5, R = –NH (CH2) 3–NH (CH2) 4–NH2); and Bleomycin A6, R = –NH (CH2) 3–NH (CH2) 4–NH (CH2) 3–NH2), often abbreviated BLM and produced by Streptomyces verticillus, are DNA strand-breaking agents that exploit their interaction with Fe (II) ion. More than two-hundred bleomycins have been isolated from different strains of Streptomyces, with molecular weights ranging from 1000 to 10,000. Bleomycin’s activity is associated with single-strand DNA cleavage through the generation of hydroxyl free radicals. Although the exact in vivo mechanism of bleomycin’s action as an antineoplastic agent is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with lesser effects arising from effects on RNA and protein synthesis. Bleomycin can stop the cell cycle at G2 and is often used to induce synchrony in cell cultures. Primary Mode of Action: Bleomycin forms chelation complexes with Fe2+, Co2+, Cu2+, Ni2+, and Zn2+. Upon binding of a bleomycin-Fe2+-O2 complex to DNA, the coplanar bithiazole moiety intercalates in the minor groove of DNA, whereupon the iron is oxidized to Fe3+, and the resulting complex of bleomycin acts on deoxyribose. Bleomycin interacts with either Fe (II) and O2 or Fe (III) and H2O2 to form an activated complex that attacks DNA. Under aerobic conditions, both reactions yield similar quantities of free bases as well as products consisting of the base plus deoxyribose carbon-atoms 1 to 3. Under anaerobic conditions, activated bleomycin releases only free base. The yield of free base is the same under aerobic or anaerobic conditions, when DNA is in excess. When DNA concentration is limiting, more base is released under anaerobic than under aerobic conditions. Drug self-destruction proceeds as quickly and completely in the presence or absence of O2. Pharmacokinetics: Bleomycin is rapidly absorbed following intramuscular (IM) or subcutaneous (SC), administration reaching peak plasma concentrations in 30 to 60 minutes and exhibiting a systemic bioavailability of 100% (IM) and 70% (SC). Upon IV bolus administration, bleomycin is widely distributed, with a mean volume of distribution of 17.5 L/m2. Protein binding has not been studied. Bleomycin is inactivated by a cytosolic cysteine proteinase enzyme, bleomycin hydrolase, which is widely distributed in normal tissues (exception: skin and lungs, where toxicity is highest. Target (s) : DNA polymerase; protein-glutamine g- glutamyltransferase (transglutaminase), by bleomycin alone or copper- bleomycin; RNA polymerase; DNA ligase; dopamine b- monooxygenase; tyrosine monooxygenase.

Raw materials

Preparation Products