Cytotoxic antibiotics lymphomas

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Doxorubicin and dannorabicin are antibiotics made from microorganisms of the family Streptomyces peucetius. The stmcture of these anthracyclines contains an aminosaccarhide residue daunozamine attached to a naphthacenequinone nucleus. Doxorubicin differs from daunorubicin in the presence of a hydroxyl gronp at C14. A nnmber of mechanisms have been suggested in which anthracyclines exhibit cytotoxicity. They canse DNA to denature, are involved in oxidation-rednction reactions, chelate bivalent cations and react with cell membranes, changing their fnnction. They are used for severe leukemia, lymphoma, breast and ovarian cancer, and other solid tumors. 

Its unusual challenging structure and significant anticancer and antibiotic activity have attracted the attention of many research groups. More than 200 papers, including reviews (77-81), have appeared so far on its synthesis, cytotoxic mechanism of action, and biosynthesis. This highly active compound against experimental lymphomas was subjected to clinical trials, but its severe toxicity to the hematopoietic system prevented its acceptance into human medicine (82). 

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