Showdomycin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-03453 |
| CAS | 16755-07-0 |
| Molecular Weight | 229.19 |
| Molecular Formula | C9H11NO6 |
| Purity | ≥ 97% |
Online Inquiry
Description
Showdomycin is a nucleoside antibiotic produced by the strain of Str. showdoensis Z-452. It has anti-bacterial effect. 5-15 mg/(kg.d) of Showdomycin can inhibit Ehrlich ascites cancer. It is also cytotoxic to HeLa cells.
Specification
| Synonyms | D-Showdomycin; 2-beta-D-Ribofuranosylmaleimide; NSC 93047; 3-beta-D-Ribofuranosyl-1H-pyrrole-2,5-dione; Maleimide, 2-b-D-ribofuranosyl-; (+)-Showdomycin; D-(+)-Showdomycin |
| IUPAC Name | 3-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrole-2,5-dione |
| Canonical SMILES | C1=C(C(=O)NC1=O)C2C(C(C(O2)CO)O)O |
| InChI | 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 |
| InChI Key | FFLUMYXAPXARJP-JBBNEOJLSA-N |
Properties
| Appearance | White Acicular Crystal |
| Application | Antibiotics, Antineoplastic |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Boiling Point | 562.4°C at 760 mmHg |
| Melting Point | 153-154°C |
| Density | 1.697 g/cm3 |
| Solubility | Soluble in Water |
Reference Reading
1. Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC 15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics
Kaisa Palmu, Petja Rosenqvist, Keshav Thapa, Yulia Ilina, Vilja Siitonen, Bikash Baral, Janne Mäkinen, Georgi Belogurov, Pasi Virta, Jarmo Niemi, Mikko Metsä-Ketelä ACS Chem Biol. 2017 Jun 16;12(6):1472-1477. doi: 10.1021/acschembio.7b00078. Epub 2017 Apr 27.
Nucleoside antibiotics are a large class of pharmaceutically relevant chemical entities, which exhibit a broad spectrum of biological activities. Most nucleosides belong to the canonical N-nucleoside family, where the heterocyclic unit is connected to the carbohydrate through a carbon-nitrogen bond. However, atypical C-nucleosides were isolated from Streptomyces bacteria over 50 years ago, but the molecular basis for formation of these metabolites has been unknown. Here, we have sequenced the genome of S. showdoensis ATCC 15227 and identified the gene cluster responsible for showdomycin production. Key to the detection was the presence of sdmA, encoding an enzyme of the pseudouridine monophosphate glycosidase family, which could catalyze formation of the C-glycosidic bond. Sequence analysis revealed an unusual combination of biosynthetic genes, while inactivation and subsequent complementation of sdmA confirmed the involvement of the locus in showdomycin formation. The study provides the first steps toward generation of novel C-nucleosides by pathway engineering.
2. Identification of a Pyrrole Intermediate Which Undergoes C-Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis
Daan Ren, Minje Kim, Shao-An Wang, Hung-Wen Liu Angew Chem Int Ed Engl. 2021 Jul 26;60(31):17148-17154. doi: 10.1002/anie.202105667. Epub 2021 Jun 24.
Showdomycin is a C-nucleoside bearing an electrophilic maleimide base. Herein, the biosynthetic pathway of showdomycin is presented. The initial stages of the pathway involve non-ribosomal peptide synthetase (NRPS) mediated assembly of a 2-amino-1H-pyrrole-5-carboxylic acid intermediate. This intermediate is prone to air oxidation whereupon it undergoes oxidative decarboxylation to yield an imine of maleimide, which in turn yields the maleimide upon acidification. It is also shown that this pyrrole intermediate serves as the substrate for the C-glycosidase SdmA in the pathway. After coupling with ribose 5-phosphate, the resulting C-nucleoside undergoes a similar sequence of oxidation, decarboxylation and deamination to afford showdomcyin after exposure to air. These results suggest that showdomycin could be an artifact due to aerobic isolation; however, the autoxidation may also serve to convert an otherwise inert product of the biosynthetic pathway to an electrophilic C-nucleotide thereby endowing showdomycin with its observed bioactivities.
3. The role of the maleimide ring system on the structure-activity relationship of showdomycin
Petja Rosenqvist, Janne J Mäkinen, Kaisa Palmu, Johanna Jokinen, Ranjit K Prajapati, Heidi J Korhonen, Pasi Virta, Georgiy A Belogurov, Mikko Metsä-Ketelä Eur J Med Chem. 2022 Jul 5;237:114342. doi: 10.1016/j.ejmech.2022.114342. Epub 2022 Apr 11.
Showdomycin produced by Streptomyces showdoensis ATCC 15227 is a C-nucleoside microbial natural product with antimicrobial and cytotoxic properties. The unique feature of showdomycin in comparison to other nucleosides is its maleimide base moiety, which has the distinct ability to alkylate nucleophilic thiol groups by a Michael addition reaction. In order to understand structure-activity relationships of showdomycin, we synthesized a series of derivatives with modifications in the maleimide ring at the site of alkylation to moderate its reactivity. The showdomycin congeners were designed to retain the planarity of the base ring system to allow Watson-Crick base pairing and preserve the nucleosidic character of the compounds. Consequently, we synthesized triphosphates of showdomycin derivatives and tested their activity against RNA polymerases. Bromo, methylthio, and ethylthio derivatives of showdomycin were incorporated into RNA by bacterial and mitochondrial RNA polymerases and somewhat less efficiently by the eukaryotic RNA polymerase II. Showdomycin derivatives acted as uridine mimics and delayed further extension of the RNA chain by multi-subunit, but not mitochondrial RNA polymerases. Bioactivity profiling indicated that the mechanism of action of ethylthioshowdomycin was altered, with approximately 4-fold reduction in both cytotoxicity against human embryonic kidney cells and antibacterial activity against Escherichia coli. In addition, the ethylthio derivative was not inactivated by medium components or influenced by addition of uridine in contrast to showdomycin. The results explain how both the maleimide ring and the nucleoside nature contribute to the bioactivity of showdomycin and demonstrates for the first time that the two activities can be separated.
Recommended Products
| BBF-02614 | Nystatin | Inquiry |
| BBF-03754 | CASTANOSPERMINE | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
