Anthramycin is a

pyrrolobenzodiazepine Pyrrolobenzodiazepines, (PBD) are a class of compound that may have antibiotic or anti-tumor properties. Some dimeric pyrrolobenzodiazepines are used as the cytotoxic drug payloads in antibody-drug conjugate Antibody-drug conjugates or ADCs ar ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

with

antitumor Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...

activity. First derived from the

thermophilic A thermophile is an organism—a type of extremophile—that thrives at relatively high temperatures, between . Many thermophiles are archaea, though they can be bacteria or fungi. Thermophilic eubacteria are suggested to have been among the ear ...

actinomycete The Actinomycetales is an order of Actinomycetota. A member of the order is often called an actinomycete. Actinomycetales are generally gram-positive and anaerobic and have mycelia in a filamentous and branching growth pattern. Some actinomycetes ...

''Streptomyces refuineus'' by M. D. Tendler and S Korman in the 1950s, it was first successfully synthesized in a laboratory setting by Leimgruber ''et al.'' in 1965. Due to the unstable nature of the chemical structure, characterization of the species was done on its

epimer In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization is ...

, anthrmycin-11-methyl-ether. This derivative can be formed by recrystallization of anthramycin from hot methanol.

Chemical structure

The chemical structure of anthramycin was first elucidated by Leimgruber using

nuclear magnetic resonance Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...

and

ultraviolet spectroscopy Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...

. Using another similarly structured fermentation product simply referred to as 'yellow pigment' as a basis of comparison, he was able to identify all major functional groups of the structure. The structure of the species was narrowed down to one of two possible candidates: one with a pyrrolobenzodiazepine nucleus, and another with a pyridoquinazoline skeleton. The first structure was confirmed through the use of

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is u ...

Medical uses

Anthramycin is an active anti-tumor agent and antibiotic. It works by inhibiting the synthesis of

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

and DNA of carcinoma cells. It is a competitive inhibitor of cell-free RNA and DNA synthesis, and blocks the action of

DNase I Deoxyribonuclease I (usually called DNase I), is an endonuclease of the DNase family coded by the human gene DNASE1. DNase I is a nuclease that cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding ...

. Anthramycin-methyl-ether (AME) forms a complex with DNA which blocks off synthesis by prohibiting DNA binding with proper enzymes. The species is heavily

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating ...

. Anthramycin has been shown particularly effective against

sarcomas A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcoma ...

lymphomas Lymphoma is a group of tumors of the hematopoietic and lymphoid tissues, blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all su ...

, and gastrointestinal

neoplasms A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

Side effects

Use of anthramycin has been largely limited due to a cardiotoxicity so high that it limits dosing. Acute tissue

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dig ...

has also been noted at the injection site of the antibiotic, and side effect of its high cytotoxicity. Repeated injections in mice have been shown to adversely affect mitochondrial metabolism. The mice also showed abnormal

electrocardiograms Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hea ...

. As such, the side effects of such medication may outweigh the benefits. Alternatives such as

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used tog ...

are today more widely available and prescribed, due to more mild side effects along with increased anti-tumor action.

References

Acrylamides Antibiotics Antineoplastic drugs Pyrrolobenzodiazepines {{Benzodiazepines

Chemical structure

Medical uses

Side effects

See also

References