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Identification
Name Quinupristin
Accession Number DB01369
Type small molecule
Groups approved
Description

Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis. The combination of the two components acts synergistically and is more effective in vitro than each component alone.

Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names Not Available
Brand name mixtures
  • Synercid (Dalfopristin + Quinupristin)
Categories
  • Antibacterial Agents
CAS number 120138-50-3
Weight Average: 1022.218
Monoisotopic: 1021.473160099
Chemical Formula C53H67N9O10S
InChI Key InChIKey=WTHRRGMBUAHGNI-MJWHERSYSA-N
InChI
InChI=1S/C53H67N9O10S/c1-6-37-50(68)61-23-11-14-38(61)51(69)59(5)40(26-32-16-18-36(19-17-32)58(3)4)52(70)62-28-35(30-73-43-29-60-24-20-33(43)21-25-60)42(64)27-39(62)47(65)57-45(34-12-8-7-9-13-34)53(71)72-31(2)44(48(66)55-37)56-49(67)46-41(63)15-10-22-54-46/h7-10,12-13,15-19,22,31,33,35,37-40,43-45,63H,6,11,14,20-21,23-30H2,1-5H3,(H,55,66)(H,56,67)(H,57,65)/t31-,35?,37-,38+,39?,40+,43-,44+,45+/m1/s1
Plain Text
IUPAC Name
N-[(3S,6S,12R,15S,16R,19S)-25-{[(3S)-1-azabicyclo[2.2.2]octan-3-ylsulfanyl]methyl}-3-{[4-(dimethylamino)phenyl]methyl}-12-ethyl-4,16-dimethyl-2,5,11,14,18,21,24-heptaoxo-19-phenyl-17-oxa-1,4,10,13,20-pentaazatricyclo[20.4.0.0^{6,10}]hexacosan-15-yl]-3-hydroxypyridine-2-carboxamide
SMILES
CC[C@H]1NC(=O)[C@@H](NC(=O)C2=C(O)C=CC=N2)[C@@H](C)OC(=O)[C@@H](NC(=O)C2CC(=O)C(CS[C@@H]3CN4CCC3CC4)CN2C(=O)[C@H](CC2=CC=C(C=C2)N(C)C)N(C)C(=O)[C@@H]2CCCN2C1=O)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the treatment of bacterial infections (usually in combination with dalfopristin).
Pharmacodynamics Quinupristin is a streptogramin antibiotic, derived from pristinamycin I. By inhibiting the bacterial ribosomal subunits, protein synthesis is inhibited thus leading to eventual bacterial cell death or stasis.
Mechanism of action Quinupristin inhibits the late phase of protein synthesis in the bacterial ribosome. Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transferase. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide as well as causing incomplete chains to be released.
Absorption Not Available
Volume of distribution Not Available
Protein binding Moderate.
Metabolism

Quinupristin is converted to two conjugated active major metabolites, one with glutathione and one with cysteine.

Route of elimination Not Available
Half life 3.1 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 4.45e-02 g/l ALOGPS
logP 2.99 ALOGPS
logP 1.97 ChemAxon Molconvert
logS -4.36 ALOGPS
pKa 11.47 ChemAxon Molconvert
hydrogen acceptor count 12 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 231.20 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 272.84 ChemAxon Molconvert
polarizability 107.02 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Allington DR, Rivey MP: Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001 Jan;23(1):24-44. Pubmed
  2. Lamb HM, Figgitt DP, Faulds D: Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs. 1999 Dec;58(6):1061-97. Pubmed
  3. Manzella JP: Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Physician. 2001 Dec 1;64(11):1863-6. Pubmed
  4. Paradisi F, Corti G, Messeri D: Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. Med Clin North Am. 2001 Jan;85(1):1-17. Pubmed
External Links
Resource Link
KEGG Drug D00852 Link_out
KEGG Compound C08032 Link_out
Therapeutic Targets Database DAP001288 Link_out
PharmGKB PA451215 Link_out
HET SYB Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Quinupristin Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (67.1 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. 23S rRNA

Pharmacological action: yes
Actions: inhibitor

In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit.

Gene Sequence: FASTA

References:
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. Pubmed
  2. Beyer D, Pepper K: The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9. Pubmed
  3. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. Pubmed
  4. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. Pubmed

2. 50S ribosomal protein L10

Pharmacological action: yes
Actions: inhibitor

Protein L10 is also a translational repressor protein. It controls the translation of the rplJL-rpoBC operon by binding to its mRNA

Organism class: bacterial
UniProt ID: P0A7J6 Link_out
Gene: rplJ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. Pubmed
  2. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. Pubmed
  3. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. Pubmed

3. 50S ribosomal protein L22

Pharmacological action: yes
Actions: inhibitor

The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome (By similarity)

Organism class: bacterial
UniProt ID: P61177 Link_out
Gene: rplV
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Barthel D, Schlitzer M, Pradel G: Telithromycin and quinupristin-dalfopristin induce delayed death in Plasmodium falciparum. Antimicrob Agents Chemother. 2008 Feb;52(2):774-7. Epub 2007 Dec 3. Pubmed
  2. Harms JM, Schlunzen F, Fucini P, Bartels H, Yonath A: Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004 Apr 1;2:4. Pubmed
  3. Dang V, Nanda N, Cooper TW, Greenfield RA, Bronze MS: Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins. J Okla State Med Assoc. 2007 Mar;100(3):75-81. Pubmed
  4. Halling SM, Jensen AE: Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC Microbiol. 2006 Oct 2;6:84. Pubmed
  5. Tu D, Blaha G, Moore PB, Steitz TA: Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. Pubmed
  6. Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A: Structural basis for the antibiotic activity of ketolides and azalides. Structure. 2003 Mar;11(3):329-38. Pubmed
  7. Petropoulos AD, Kouvela EC, Starosta AL, Wilson DN, Dinos GP, Kalpaxis DL: Time-resolved binding of azithromycin to Escherichia coli ribosomes. J Mol Biol. 2009 Jan 30;385(4):1179-92. Epub 2008 Nov 27. Pubmed
  8. Champney WS, Miller M: Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. Curr Microbiol. 2002 Jun;44(6):418-24. Pubmed

Comments
Drug created on July 06, 2007 14:25 / Updated on December 24, 2010 15:17

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.