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Identification
Name Colistin
Accession Number DB00803 (APRD00886)
Type small molecule
Groups approved
Description

Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Colistin sulfate
Colistin sulfate, nonsterile
Colistin sulphate
Polymyxin E sulfate
Polymyxin E. Sulfate
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
CAS number 1264-72-8
Weight Average: 1155.4339
Monoisotopic: 1154.749927302
Chemical Formula C52H98N16O13
InChI Key InChIKey=YKQOSKADJPQZHB-QNPLFGSASA-N
InChI
InChI=1S/C52H98N16O13/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1
Plain Text
IUPAC Name
N-[(1S)-3-amino-1-{[(1S,2R)-1-{[(1S)-3-amino-1-{[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptaazacyclotricosan-21-yl]carbamoyl}propyl]carbamoyl}-2-hydroxypropyl]carbamoyl}propyl]-5-methylheptanamide
SMILES
[H][C@]1(NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC(=O)[C@H](CCNC1=O)NC(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)CCCC(C)CC)[C@@H](C)O)[C@@H](C)O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Lactams
  • Alcohols and Polyols
Substructures
  • Polypeptides
  • Hydroxy Compounds
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Alcohols and Polyols
Pharmacology
Indication For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa.
Pharmacodynamics Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.
Mechanism of action Colistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.
Absorption Very poor absorption from gastrointestinal tract.
Volume of distribution Not Available
Protein binding Not Available
Metabolism
As 80% of the dose can be recovered unchanged in the urine, and there is no biliary excretion, it can be assumed that the remaining drug is inactivated in the tissues, however the mechanism is unknown.
Route of elimination Not Available
Half life 5 hours
Clearance Not Available
Toxicity Oral LD50 in rats is 5450 mg/kg. Overdosage with colistimethate can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death.
Affected organisms
  • Gram-negative bacilli
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Colistin sulfate powder 513.26 USD each
Coly-Mycin S 3.3-3-10 mg/ml Suspension 5ml Bottle 49.17 USD bottle
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 200-220 °C Not Available
water solubility 5.64E+005 mg/L Not Available
logP -2.4 Not Available
Predicted Properties
Property Value Source
water solubility 2.38e-01 g/l ALOGPS
logP -1.3 ALOGPS
logP -8.1 ChemAxon
logS -3.7 ALOGPS
pKa (strongest acidic) 11.6 ChemAxon
pKa (strongest basic) 10.23 ChemAxon
physiological charge 5 ChemAxon
hydrogen acceptor count 18 ChemAxon
hydrogen donor count 18 ChemAxon
polar surface area 490.66 ChemAxon
rotatable bond count 28 ChemAxon
refractivity 297.67 ChemAxon
polarizability 125.93 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02138 Link_out
KEGG Compound C13768 Link_out
PubChem Compound 5311054 Link_out
PubChem Substance 46505467 Link_out
ChemSpider 4470591 Link_out
Therapeutic Targets Database DAP001324 Link_out
PharmGKB PA164760862 Link_out
Wikipedia http://en.wikipedia.org/wiki/Colistin Link_out
ATC Codes
  • J01XB01
  • A07AA10
AHFS Codes
  • 08:12.28.28
PDB Entries Not Available
FDA label Not Available
MSDS show (72.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. bacterial outer membrane

Pharmacological action: yes
Actions: incorporation into and destabilization

References:
  1. Vaara M: Polymyxins and their novel derivatives. Curr Opin Microbiol. 2010 Oct;13(5):574-81. Epub 2010 Sep 24. Pubmed
  2. Soon RL, Nation RL, Cockram S, Moffatt JH, Harper M, Adler B, Boyce JD, Larson I, Li J: Different surface charge of colistin-susceptible and -resistant Acinetobacter baumannii cells measured with zeta potential as a function of growth phase and colistin treatment. J Antimicrob Chemother. 2011 Jan;66(1):126-33. Epub 2010 Nov 16. Pubmed
  3. Evans ME, Feola DJ, Rapp RP: Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999 Sep;33(9):960-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19