ATC Group: L01D Cytotoxic antibiotics and related substances

Aclarubicin is an anthracycline antibiotic produced by Streptomyces galilaeus and also has potent antineoplastic activity. It is less cardiotoxic than doxorubicin and daunorubicin. The mechanism of action of aclarubicin is based on its capacity to insert its trisaccharide chain into the minor DNA groove: poison of topoisomerase I, inhibitor of topoisomerase II, eviction of histones from nucleosomes, but also inhibitor of the 20S proteasome.

Bleomycin is a mixture of basic, water-soluble glycopeptide-antibiotics with cytotoxic activity. Bleomycin acts by interacting with both single and double-stranded DNA (deoxyribonucleic acid) leading to both single and double-strand scission, which leads in turn to inhibition of cell division, inhibition of growth and inhibition of DNA synthesis. Bleomycin can also influence RNA (ribonucleic acid) and protein biosynthesis to a lesser extent.

Dactinomycin is an antineoplastic antibiotic derived from Streptomyces parvullus. Stable complexes are formed with DNA through intercalation and DNA-dependent RNA synthesis is selectively inhibited. Protein and DNA synthesis are inhibited to a lesser extent.

Daunorubicin is an anthracycline glycoside antibiotic and is a potent antileukaemic agent. It also has immunosuppressant effects. Daunorubicin may involve binding to DNA by intercalation between base pairs and inhibition of DNA and RNA synthesis by template disordering and steric obstruction.

Doxorubicin is a cytotoxic anthracycline antibiotic obtained from Streptomyces peucetius var. caesius. The exact mechanism of the antitumour activity of doxorubicin is not known. It is generally believed that inhibition of DNA, RNA and protein synthesis is responsible for the majority of the cytotoxic effects.

Epirubicin is a cytotoxic active antibiotic from the anthracycline group. The mechanism of action of epirubicin is related to its ability to bind to DNA. Cell culture studies have shown rapid cell penetration, localisation in the nucleus and inhibition of nucleic acid synthesis and mitosis.

Idarubicin is a DNA intercalating anthracycline which interacts with the enzyme topoisomerase II and has an inhibitory effect on nucleic acid synthesis. Idarubicin has been shown to have a higher potency with respect to daunorubicin and to be an effective agent against murine leukaemia and lymphomas both by i.v. and oral routes.

Mitomycin is an antibiotic isolated from Streptomyces caespitosus with anti-neoplastic effect. The mechanism of action is based predominantly on the alkylation of DNA (RNA to a lesser extent) with the corresponding inhibition of DNA synthesis. The degree of DNA damage correlates with the clinical effect and is lower in resistant cells than in sensitive ones.

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA.

Pixantrone is a cytotoxic aza-anthracenedione. Unlike approved anthracyclines (doxorubicin and others) and anthracenediones (mitoxantrone), pixantrone is only a weak inhibitor of topoisomerase II. Pixantrone is indicated as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin B-cell lymphomas (NHL).

Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G₂.