Showdomycin is a

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...

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 ...

derived from ''

Streptomyces showdoensis ''Streptomyces showdoensis'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil in Shōdoshima, Japan.Deutsche Sammlung von Mikroorganismen und Zellkulturen The Leibniz Institute DSMZ - German Collect ...

''. It is known for its antitumor and

antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...

properties. Showdomycin was first isolated in the 1960s and has since been studied for its potential applications in

cancer research Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure. Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate ...

and

microbiology Microbiology () is the branches of science, scientific study of microorganisms, those being of unicellular organism, unicellular (single-celled), multicellular organism, multicellular (consisting of complex cells), or non-cellular life, acellula ...

Discovery and History

Showdomycin was first discovered in 1964 by Japanese researchers during a screening of ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' species for novel antibiotics. It was isolated from ''Streptomyces showdoensis'', a soil

bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...

, and its structure was elucidated shortly thereafter. The compound gained attention for its unusual structure, which includes a maleimide ring fused to a

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

sugar, distinguishing it from other nucleoside antibiotics.

Chemical Structure

Showdomycin is a C-nucleoside, meaning the sugar is directly bonded to a

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atom of the maleimide ring rather than a

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atom, as seen in typical nucleosides. Its chemical formula is C₉H₁₁NO₆, and its systematic name is 1-β-D-ribofuranosyl-1H-pyrrole-2,5-dione. The maleimide moiety is responsible for its reactivity, particularly its ability to act as a Michael acceptor in biochemical reactions. It displays a high similarity with

uridine Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1- glycosidic bond. The analog is one of the five standard nucleosides which make up nuc ...

and pseudouridine.

Mechanism of Action

Showdomycin exhibits its biological activity through several mechanisms: *Inhibition of Enzymes: It is a Sulfhydryl reagent and acts as an irreversible inhibitor of certain enzymes, particularly those with thiol groups, by forming

covalent bonds A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

with cysteine residues. *Antitumor Activity: Showdomycin and its derivatives act as uridine mimics, thereby delaying RNA extension and hence RNA synthysis. This makes it effective against rapidly dividing cancer cells. *Antimicrobial Activity: It inhibits the growth of various

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

and bacteria, especially '' Streptococcus hemolyticus'' and ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' by disrupting essential metabolic pathways.

Applications

Showdomycin is a compound commonly used in biochemical research to investigate enzyme mechanisms and protein interactions. It works by selectively modifying thiol groups, making it a valuable tool for studying protein structure and function. Although it has not been developed into a commercial drug, researchers have explored its potential therapeutic uses. Preclinical studies have shown that showdomycin possesses both antitumor and antimicrobial properties. It has demonstrated effectiveness against certain antibiotic-resistant pathogens, making it a potential candidate for future drug development. However its use in therapeutic applications is limited by its lack of selectivity, which can lead to adverse effects on healthy cells.

References

{{reflist Antibiotics Succinimides Ribosides