Showdomycin

Showdomycin was first discovered in 1964 by Japanese researchers during a screening of Streptomyces species for novel antibiotics. It was isolated from Streptomyces showdoensis, a soil bacterium, and its structure was elucidated shortly thereafter. The compound gained attention for its unusual structure, which includes a maleimide ring fused to a ribose sugar, distinguishing it from other nucleoside antibiotics.{{Cite journal |last1=Palmu |first1=Kaisa |last2=Rosenqvist |first2=Petja |last3=Thapa |first3=Keshav |last4=Ilina |first4=Yulia |last5=Siitonen |first5=Vilja |last6=Baral |first6=Bikash |last7=Mäkinen |first7=Janne |last8=Belogurov |first8=Georgi |last9=Virta |first9=Pasi |last10=Niemi |first10=Jarmo |last11=Metsä-Ketelä |first11=Mikko |date=2017-06-16 |title=Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC 15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics |url=https://pubmed.ncbi.nlm.nih.gov/28418235/ |journal=ACS Chemical Biology |volume=12 |issue=6 |pages=1472–1477 |doi=10.1021/acschembio.7b00078 |issn=1554-8937 |pmid=28418235}}

Showdomycin is a C-nucleoside, meaning the sugar is directly bonded to a carbon atom of the maleimide ring rather than a nitrogen 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.{{Cite journal |last=Koshland |first=Daniel E. |date=1968-03-08 |title=Enzyme Specificity: Design of Active-Site-Directed Irreversible Enzyme Inhibitors. The Organic Chemistry of the Enzymic Active-Site. B. R. Baker. Wiley, New York, 1967. xvi + 325 pp., illus. $13.50. |url=https://www.science.org/doi/10.1126/science.159.3819.1091.b |journal=Science |volume=159 |issue=3819 |pages=1091 |doi=10.1126/science.159.3819.1091.b|url-access=subscription }} It displays a high similarity with uridine and pseudouridine.{{Cite journal |last1=Böttcher |first1=Thomas |last2=Sieber |first2=Stephan A. |date=2010-05-26 |title=Showdomycin as a versatile chemical tool for the detection of pathogenesis-associated enzymes in bacteria |url=https://pubmed.ncbi.nlm.nih.gov/20433172/ |journal=Journal of the American Chemical Society |volume=132 |issue=20 |pages=6964–6972 |doi=10.1021/ja909150y |issn=1520-5126 |pmid=20433172|bibcode=2010JAChS.132.6964B }}{{Cite journal |last1=Darnall |first1=K. R. |last2=Townsend |first2=Leroy B. |last3=Robins |first3=Roland K. |date=1967-03-01 |title=The structure of showdomycin, a novel carbon-linked nucleoside antibiotic related to uridine* |journal=Proceedings of the National Academy of Sciences |volume=57 |issue=3 |pages=548–553 |doi=10.1073/pnas.57.3.548 |doi-access=free |pmc=335542 |pmid=16591497|bibcode=1967PNAS...57..548D }}

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 with cysteine residues.{{Citation |last=Shaw |first=Elliott |title=2 Chemical Modification by Active-Site-Directed Reagents* |date=1970-01-01 |series=The Enzymes |volume=1 |pages=91–146 |editor-last=Boyer |editor-first=Paul D. |url=https://linkinghub.elsevier.com/retrieve/pii/S1874604708601651 |access-date=2025-01-28 |publisher=Academic Press |doi=10.1016/s1874-6047(08)60165-1|isbn=978-0-12-122701-2 |url-access=subscription }}
• 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.{{Cite journal |last1=Numao |first1=N. |last2=Hemmi |first2=H. |last3=Naujokaitis |first3=S. A. |last4=Rabinovitz |first4=M. |last5=Beisler |first5=J. A. |date=1981-05-01 |title=Showdomycin analogues: synthesis and antitumor evaluation |url=https://pubmed.ncbi.nlm.nih.gov/7241509/ |journal=Journal of Medicinal Chemistry |volume=24 |issue=5 |pages=515–520 |doi=10.1021/jm00137a008 |issn=0022-2623 |pmid=7241509}}
• Antimicrobial Activity: It inhibits the growth of various fungi and bacteria, especially Streptococcus hemolyticus and Streptococcus pyogenes{{Cite journal |last1=Roy-Burman |first1=S. |last2=Roy-Burman |first2=P. |last3=Visser |first3=D. W. |date=1968-08-01 |title=Showdomycin, A New Nucleoside Antibiotic1 |url=https://aacrjournals.org/cancerres/article/28/8/1605/477106/Showdomycin-A-New-Nucleoside-Antibiotic1 |journal=Cancer Research |volume=28 |issue=8 |pages=1605–1610 |pmid=5691758 |issn=0008-5472}} by disrupting essential metabolic pathways.{{Cite journal |last=Blaschke |first=G. |date=1979 |title=The Chemistry of the Tetracycline Antibiotics (Medicinal Research Series, Vol. 9) von L. A. Mitscher, 352 S., Preis 82,— SFr., Marcel Dekker, Inc., New York 1978 |url=https://onlinelibrary.wiley.com/doi/10.1002/ardp.19793120814 |journal=Archiv der Pharmazie |language=en |volume=312 |issue=8 |pages=719 |doi=10.1002/ardp.19793120814 |issn=1521-4184|url-access=subscription }}

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.

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Category:Antibiotics

Category:Succinimides

Category:Ribosides