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colistin
Also known as: Colistin, 1066-17-7, N-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-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-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-5-methylheptanamide, Colobreathe, Promixin, Colistin,(s)
Molecular Formula
C52H98N16O13
Molecular Weight
1155.4  g/mol
InChI Key
YKQOSKADJPQZHB-QNPLFGSASA-N

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.
1 2D Structure

colistin

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-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-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-5-methylheptanamide
2.1.2 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
2.1.3 InChI Key
YKQOSKADJPQZHB-QNPLFGSASA-N
2.1.4 Canonical SMILES
CCC(C)CCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC1=O)CCN)CC(C)C)CC(C)C)CCN)CCN)C(C)O
2.1.5 Isomeric SMILES
CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC1=O)CCN)CC(C)C)CC(C)C)CCN)CCN)[C@@H](C)O
2.2 Synonyms
2.2.1 MeSH Synonyms

1. Colimycin

2. Colisticin

3. Colistin

4. Colistin Sulfate

5. Coly-mycin

6. Sulfate, Colistin

7. Totazina

2.2.2 Depositor-Supplied Synonyms

1. Colistin

2. 1066-17-7

3. N-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-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-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-5-methylheptanamide

4. Colobreathe

5. Promixin

6. Colistin,(s)

7. Chembl499783

8. Schembl1979092

9. Gtpl10794

10. Colistin Sulfate, >19000 Iu/mg

11. Ab01566924_01

12. 066c177

13. Q418946

14. Sr-01000872582

15. Sr-01000872582-1

16. 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-diisobutyl-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]carbamoyl]propyl]carbamoyl]-2-hydroxy-propyl]carbamoyl]propyl]-5-methyl-heptanamide

17. 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

2.3 Create Date
2005-12-16
3 Chemical and Physical Properties
Molecular Weight 1155.4 g/mol
Molecular Formula C52H98N16O13
XLogP3-3.3
Hydrogen Bond Donor Count18
Hydrogen Bond Acceptor Count18
Rotatable Bond Count28
Exact Mass1154.74992724 g/mol
Monoisotopic Mass1154.74992724 g/mol
Topological Polar Surface Area491 Ų
Heavy Atom Count81
Formal Charge0
Complexity2050
Isotope Atom Count0
Defined Atom Stereocenter Count12
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Antibiotics, Peptide

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


THERAPEUTIC INDICATIONS FOR COLISTIN ARE ESSENTIALLY SAME AS THOSE FOR POLYMYXIN B. INFECTIONS OF CERTAIN TYPES CAUSED BY PSEUD AERUGINOSA ARE ESPECIALLY SUSCEPTIBLE.

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


PRIMARY USE OF POLYMYXIN B IS FOR TREATMENT OF INFECTIONS CAUSED BY GRAM-NEGATIVE BACTERIA, ESPECIALLY PSEUDOMONAS. ...IS EFFECTIVE IN TREATMENT OF URINARY TRACT INFECTIONS CAUSED BY PSEUDOMONAS OR OTHER GRAM-NEGATIVE BACILLI RESISTANT TO OTHER ANTIMICROBIAL AGENTS... /POLYMYXIN B/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1232


/POLYMYXIN B & COLISTIMETHATE SODIUM/...RECOMMENDED FOR TREATING PERITONITIS & PNEUMONIA, BUT SOME AUTHORITIES QUESTION THEIR EFFECTIVENESS FOR THESE PURPOSES. /COLISTIMETHATE SODIUM/

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 734


For more Therapeutic Uses (Complete) data for COLISTIN (11 total), please visit the HSDB record page.


4.2 Drug Warning

ADVERSE REACTIONS TO COLISTIMETHATE HAVE BEEN NOTED IN 20% OF PT GIVEN THE DRUG; THEY ARE GENERALLY REVERSIBLE... /COLISTIMETHATE/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


COLISTIMETHATE SODIUM SHOULD NOT BE ADMIN INTRATHECALLY. /COLISTIMETHATE SODIUM/

American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 734


...NOT INDICATED FOR INFECTIONS CAUSED BY PROTEUS OR NEISSERIA SPECIES. /SODIUM COLISTIMETHATE/

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 97. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1997 (Plus Supplements)., p. 394


POSSIBLE EMBRYOTOXIC & TERATOGENIC EFFECTS HAVE BEEN REPORTED WHEN COLISTIMETHATE SODIUM WAS ADMINISTERED TO PREGNANT RABBITS. /NA COLISTIMETHATE/

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 97. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1997 (Plus Supplements)., p. 395


For more Drug Warnings (Complete) data for COLISTIN (13 total), please visit the HSDB record page.


4.3 Drug Indication

Colobreathe is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF) aged six years and older.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Anti-Bacterial Agents

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)


5.2 ATC Code

J01XB01


A - Alimentary tract and metabolism

A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents

A07A - Intestinal antiinfectives

A07AA - Antibiotics

A07AA10 - Colistin


J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01X - Other antibacterials

J01XB - Polymyxins

J01XB01 - Colistin


5.3 Absorption, Distribution and Excretion

/COLISTIMETHATE SODIUM/...IS EXCRETED IN DOG URINE TO MUCH GREATER EXTENT THAN SIMPLE SULFATE FORM, & THEORETICALLY SHOULD BE BETTER IN URINARY INFECTIONS.

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 130


DRUG PASSES FROM MATERNAL TO FETAL CIRCULATION. PREMATURE INFANTS INJECTED WITH 1 MG/KG DO NOT DEVELOP EFFECTIVE PLASMA CONCN OF ANTIBIOTIC; WITH DOSE OF 2 MG/KG, PEAK VALUE OF ABOUT 5 UG/ML IS REACHED IN 30 MIN. /COLISTIMETHATE/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


PLASMA CONCN ARE HIGHER IN PERSONS WITH RENAL INSUFFICIENCY & ARE RELATED TO DEGREE OF RENAL DYSFUNCTION. COLISTIMETHATE IS EXCRETED MAINLY BY GLOMERULAR FILTRATION. URINE CONCN EXCEED 200 UG/ML DURING FIRST 2 HR AFTER USUAL IM DOSE. /COLISTIMETHATE/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


DRUG IS EXCRETED MORE RAPIDLY IN CHILDREN THAN IN ADULTS. COLISTIMETHATE DOES NOT GAIN ACCESS TO CEREBROSPINAL FLUID, EVEN WHEN MENINGES ARE INFLAMED. /COLISTIMETHATE/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


For more Absorption, Distribution and Excretion (Complete) data for COLISTIN (8 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

...hydrolyzed in vivo to colistin and possibly other metabolites with fewer substituted amino groups...

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 97. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1997 (Plus Supplements)., p. 394


AFTER IV INJECTION RABBITS, 75% DOSE EXCRETED IN URINE UNCHANGED. SMALL AMT FOUND IN BILE. COLISTIN-N-GLUCURONIDE FOUND IN URINE (1.7% OF DOSE) & BILE (6.7% OF DOSE). /SODIUM COLISTIN METHANE SULFONATE/

ABE ET AL; CHEMOTHERAPY (TOKYO) 24(8) 1592-1596 (1976)


5.5 Biological Half-Life

IM INJECTION OF 150 MG OF COLISTIMETHATE IN ADULTS PRODUCE PEAK PLASMA CONCN OF 6 UG/ML @ 2 HR; THIS DECLINES WITH HALF-TIME OF 2 HR. SAME QUANTITY GIVEN IV YIELDS MAXIMAL PLASMA CONCN OF 18 UG/ML; THIS FALLS TO ABOUT 0.4 UG/ML @ 12 HR. /COLISTIMETHATE/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1233


5.6 Mechanism of Action

POLYMYXIN B IS SURFACE-ACTIVE AGENT... CONTAINING LIPOPHILIC & LIPOPHOBIC GROUPS SEPARATED WITHIN MOLECULE. /POLYMYXIN B/

Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1144


PERMEABILITY OF THE BACTERIAL MEMBRANE CHANGES IMMEDIATELY ON CONTACT WITH DRUG. SENSITIVITY TO POLYMYXIN B APPARENTLY IS RELATED TO THE PHOSPHOLIPID CONTENT OF THE CELL WALL-MEMBRANE COMPLEX. /POLYMYXIN B/

Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1144


Colistin acts like a cationic detergent and binds to and damages the bacterial cytoplasmic membrane of susceptible bacteria. Damage to the bacterial cytoplasmic membrane alters the osmotic barrier of the membrane and causes leakage of essential intracellular metabolites and nucleosides.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 97. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1997 (Plus Supplements)., p. 394


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