DrugBank: Quinupristin (DB01369)

targets (3)

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

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

Allington DR, Rivey MP: Quinupristin/dalfopristin: a therapeutic review. Clin Ther. 2001 Jan;23(1):24-44. Pubmed
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
Manzella JP: Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Physician. 2001 Dec 1;64(11):1863-6. Pubmed
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
KEGG Compound	C08032
Therapeutic Targets Database	DAP001288
PharmGKB	PA451215
HET	SYB
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Quinupristin

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: 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 Beyer D, Pepper K: The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9. Pubmed 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 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 Gene: rplJ Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 Gene: rplV Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 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 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 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 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

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:

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
Beyer D, Pepper K: The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9. Pubmed
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
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:

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
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
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:

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
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
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
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
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
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
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
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.