Polymyxin B

Polymyxin B

Systematic (IUPAC) name
N-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris(2-aminoethyl)-15-benzyl-3-(1-hydroxyethyl)-12-(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]-6-methyloctanamide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	?
Routes	Topical
Identifiers
CAS number	1405-20-5 Y
ATC code	A07AA05 J01XB02 S01AA18 S02AA11 S03AA03 QJ51XB02
PubChem	CID 5702105
DrugBank	APRD01190
ChEMBL	CHEMBL1201283 N
NIAID ChemDB	007797
Chemical data
Formula	C56H100N16O17S
Mol. mass	1301.56 g/mol
N (what is this?)  (verify)

Polymyxin B is an antibiotic primarily used for resistant Gram-negative infections. It is derived from the bacterium Bacillus polymyxa. Polymyxin B is a mixture of two closely related compounds, polymyxin B1 and polymyxin B2. It has a bactericidal action against almost all Gram-negative bacilli except the Proteus group. Polymyxins bind to the cell membrane and alter its structure, making it more permeable. The resulting water uptake leads to cell death. Polymyxins are cationic, basic proteins that act like detergents (surfactants). Side effects include neurotoxicity and acute renal tubular necrosis. Polymyxins are used in the topical first-aid preparation Neosporin.

1. Family of polypeptides with attached fatty acid; cationic detergent at physiological pH, both hydrophilic and hydrophobic properties
2. Bactericidal for gram-negative; little to no effect on gram-positive, since cell wall is too thick to permit access to membrane

Mechanism of action

1. Alters bacterial outer membrane permeability by binding to a negatively charged site in the lipopolysaccharide layer, which has an electrostatic attraction for the positively charged amino groups in the cyclic peptide portion (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane
2. Fatty acid portion dissolves in hydrophobic region of cytoplasmic membrane and disrupts membrane integrity
3. Leakage of cellular molecules, inhibition of cellular respiration
4. Binds and inactivates endotoxin
5. Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic

Research application

In addition to its antibiotic function, polymyxin B has been used to clear endotoxin contamination in reagents.

see also

• Polymyxin