Showdomycin

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Showdomycin
Showdomycin.svg
Names
IUPAC name
(1S)-1,4-Anhydro-1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-D-ribitol
Other names
  • 2-β-D-Ribofuranosylmaleimide
  • 3-β-D-Ribofuranosyl-1H-pyrrole-2,5-dione
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
MeSH Showdomycin
PubChem CID
UNII
  • InChI=1S/C9H11NO6/c11-2-4-6(13)7(14)8(16-4)3-1-5(12)10-9(3)15/h1,4,6-8,11,13-14H,2H2,(H,10,12,15)/t4-,6-,7-,8+/m1/s1
    Key: FFLUMYXAPXARJP-JBBNEOJLSA-N
  • C1=C(C(=O)NC1=O)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O
Properties
C9H11NO6
Molar mass 229.188 g·mol−1
Melting point 153–154 °C (307–309 °F; 426–427 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Showdomycin is a nucleoside antibiotic derived from Streptomyces showdoensis . It is known for its antitumor and antimicrobial properties. [1] Showdomycin was first isolated in the 1960s and has since been studied for its potential applications in cancer research and microbiology. [2] [3]

Contents

Discovery and History

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. [4]

Chemical Structure

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. [1] [5] It displays a high similarity with uridine and pseudouridine. [6] [7]

Mechanism of Action

Showdomycin exhibits its biological activity through several mechanisms:

Applications

Showdomycin is a compound commonly used in biochemical research to investigate enzyme mechanisms and protein interactions. [6] It works by selectively modifying thiol groups, making it a valuable tool for studying protein structure and function. [1] 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. [2] It has demonstrated effectiveness against certain antibiotic-resistant pathogens, [3] [7] 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

  1. 1 2 3 4 Rosenqvist, Petja; Mäkinen, Janne J.; Palmu, Kaisa; Jokinen, Johanna; Prajapati, Ranjit K.; Korhonen, Heidi J.; Virta, Pasi; Belogurov, Georgiy A.; Metsä-Ketelä, Mikko (2022-07-05). "The role of the maleimide ring system on the structure-activity relationship of showdomycin". European Journal of Medicinal Chemistry. 237 114342. doi: 10.1016/j.ejmech.2022.114342 . ISSN   1768-3254. PMID   35439612.
  2. 1 2 Matsuura, S.; Shiratori, O.; Katagiri, K. (1964-11-01). "Antitumor Activity of Showdomycin". The Journal of Antibiotics. 17: 234–237. ISSN   0021-8820. PMID   14236202.
  3. 1 2 3 Nishimura, H.; Mayama, M.; Komatsu, Y.; Kato, H.; Shimaoka, N.; Tanaka, Y. (1964-07-01). "Showdomycin, A New Antibiotic from a Streptomyces Sp". The Journal of Antibiotics. 17: 148–155. ISSN   0021-8820. PMID   14194952.
  4. ↑ Palmu, Kaisa; Rosenqvist, Petja; Thapa, Keshav; Ilina, Yulia; Siitonen, Vilja; Baral, Bikash; Mäkinen, Janne; Belogurov, Georgi; Virta, Pasi; Niemi, Jarmo; Metsä-Ketelä, Mikko (2017-06-16). "Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC 15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics". ACS Chemical Biology. 12 (6): 1472–1477. doi:10.1021/acschembio.7b00078. ISSN   1554-8937. PMID   28418235.
  5. ↑ Koshland, Daniel E. (1968-03-08). "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" . Science. 159 (3819): 1091. doi:10.1126/science.159.3819.1091.b.
  6. 1 2 Böttcher, Thomas; Sieber, Stephan A. (2010-05-26). "Showdomycin as a versatile chemical tool for the detection of pathogenesis-associated enzymes in bacteria". Journal of the American Chemical Society. 132 (20): 6964–6972. Bibcode:2010JAChS.132.6964B. doi:10.1021/ja909150y. ISSN   1520-5126. PMID   20433172.
  7. 1 2 Darnall, K. R.; Townsend, Leroy B.; Robins, Roland K. (1967-03-01). "The structure of showdomycin, a novel carbon-linked nucleoside antibiotic related to uridine*". Proceedings of the National Academy of Sciences. 57 (3): 548–553. Bibcode:1967PNAS...57..548D. doi: 10.1073/pnas.57.3.548 . PMC   335542 . PMID   16591497.
  8. ↑ Shaw, Elliott (1970-01-01), Boyer, Paul D. (ed.), 2 Chemical Modification by Active-Site-Directed Reagents* , The Enzymes, vol. 1, Academic Press, pp. 91–146, doi:10.1016/s1874-6047(08)60165-1, ISBN   978-0-12-122701-2 , retrieved 2025-01-28
  9. ↑ Numao, N.; Hemmi, H.; Naujokaitis, S. A.; Rabinovitz, M.; Beisler, J. A. (1981-05-01). "Showdomycin analogues: synthesis and antitumor evaluation". Journal of Medicinal Chemistry. 24 (5): 515–520. doi:10.1021/jm00137a008. ISSN   0022-2623. PMID   7241509.
  10. ↑ Roy-Burman, S.; Roy-Burman, P.; Visser, D. W. (1968-08-01). "Showdomycin, A New Nucleoside Antibiotic1". Cancer Research. 28 (8): 1605–1610. ISSN   0008-5472. PMID   5691758.
  11. ↑ Blaschke, G. (1979). "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" . Archiv der Pharmazie. 312 (8): 719. doi:10.1002/ardp.19793120814. ISSN   1521-4184.
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