Identification

Name
Gramicidin D
Accession Number
DB00027  (BTD00036, BIOD00036)
Type
Small Molecule
Groups
Approved
Description

Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution.

Structure
Thumb
Synonyms
  • Bacillus brevis gramicidin D
  • Gramicidin
  • Gramicidin A
  • Gramicidin B
  • Gramicidin C
  • Gramicidina
  • Gramicidine
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Antibiotic CreamGramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalCanadian Custom Packaging Company2012-03-22Not applicableCanada
Antibiotic CreamGramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalPharmetics (2011) Inc.2009-12-23Not applicableCanada
Antibiotic CreamGramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalTechnilab Pharma Inc.1998-11-032005-08-05Canada
Antibiotic Cream for KidsGramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalTaro Pharmaceuticals, Inc.2009-07-30Not applicableCanada
Antibiotic Cream for KidsGramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalPharmetics (2011) Inc.Not applicableNot applicableCanada
Antibiotic Cream Plus Pain ReliefGramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalPharmetics (2011) Inc.2009-12-23Not applicableCanada
Antibiotic Cream Plus Pain ReliefGramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalCanadian Custom Packaging Company2012-04-09Not applicableCanada
Antibiotic Cream Plus Pain Relief for KidsGramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit)CreamTopicalCanadian Custom Packaging Company2012-07-11Not applicableCanada
Antibiotic DropsGramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit)SolutionAuricular (otic); OphthalmicSandoz Canada Incorporated2017-06-01Not applicableCanada
Antibiotic Ear DropsGramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit)Solution / dropsAuricular (otic)Sandoz Canada Incorporated2017-09-01Not applicableCanada
International/Other Brands
Sofradex (Sanofi)
Categories
UNII
5IE62321P4
CAS number
1405-97-6
Weight
Average: 1811.253
Monoisotopic: 1810.033419343
Chemical Formula
C96H135N19O16
InChI Key
NDAYQJDHGXTBJL-MWWSRJDJSA-N
InChI
InChI=1S/C96H135N19O16/c1-50(2)36-71(105-79(118)48-102-93(128)80(54(9)10)103-49-117)86(121)104-58(17)84(119)113-82(56(13)14)95(130)115-83(57(15)16)96(131)114-81(55(11)12)94(129)112-78(43-62-47-101-70-33-25-21-29-66(62)70)92(127)108-74(39-53(7)8)89(124)111-77(42-61-46-100-69-32-24-20-28-65(61)69)91(126)107-73(38-52(5)6)88(123)110-76(41-60-45-99-68-31-23-19-27-64(60)68)90(125)106-72(37-51(3)4)87(122)109-75(85(120)97-34-35-116)40-59-44-98-67-30-22-18-26-63(59)67/h18-33,44-47,49-58,71-78,80-83,98-101,116H,34-43,48H2,1-17H3,(H,97,120)(H,102,128)(H,103,117)(H,104,121)(H,105,118)(H,106,125)(H,107,126)(H,108,127)(H,109,122)(H,110,123)(H,111,124)(H,112,129)(H,113,119)(H,114,131)(H,115,130)/t58-,71+,72+,73+,74+,75-,76-,77-,78-,80-,81+,82+,83-/m0/s1
IUPAC Name
(2R)-N-[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-[(2-hydroxyethyl)carbamoyl]-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]-2-{2-[(2S)-2-formamido-3-methylbutanamido]acetamido}-4-methylpentanamide
SMILES
CC(C)C[C@@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCCO

Pharmacology

Indication

For treatment of skin lesions, surface wounds and eye infections.

Associated Conditions
Pharmacodynamics

Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution.

Mechanism of action

Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization (it acts as a channel). This leads to (i) loss of intracellular solutes (e.g., K+ and amino acids); (ii) dissipation of the transmembrane potential; (iii) inhibition of respiration; (iv) a reduction in ATP pools; and (v) inhibition of DNA, RNA, and protein synthesis, which leads to cell death.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Pseudomonas aeruginosa
  • Streptococcus pneumoniae
  • Streptococcus agalactiae
  • Neisseria meningitidis
  • Haemophilus influenzae
  • Neisseria gonorrhoeae
  • Escherichia coli
  • Staphylococcus aureus
  • Klebsiella
  • Enterobacter
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

U.S.Patent 2,534,541.

General References
  1. Ketchem RR, Lee KC, Huo S, Cross TA: Macromolecular structural elucidation with solid-state NMR-derived orientational constraints. J Biomol NMR. 1996 Jul;8(1):1-14. [PubMed:8810522]
  2. Townsley LE, Tucker WA, Sham S, Hinton JF: Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry. 2001 Oct 2;40(39):11676-86. [PubMed:11570868]
  3. Burkhart BM, Gassman RM, Langs DA, Pangborn WA, Duax WL, Pletnev V: Gramicidin D conformation, dynamics and membrane ion transport. Biopolymers. 1999;51(2):129-44. [PubMed:10397797]
External Links
KEGG Drug
D04369
PubChem Compound
45267103
PubChem Substance
46507412
ChemSpider
24623445
ChEMBL
CHEMBL557217
Therapeutic Targets Database
DAP001327
PharmGKB
PA449808
Wikipedia
Gramicidin_D
ATC Codes
R02AB30 — Gramicidin
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Unknown StatusTreatmentHordeolum1
Not AvailableCompletedTreatmentNasal Carriers of Staphylococcus Aureus1
Not AvailableWithdrawnPreventionBlood Stream Infections / Skin Diseases, Infectious1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Johnson & Johnson Healthcare
  • Monarch Pharmacy
  • Professional Co.
Dosage forms
FormRouteStrength
Solution / dropsAuricular (otic)
Solution / dropsOphthalmic
SolutionOphthalmic
SolutionAuricular (otic); Ophthalmic
LiquidOphthalmic
LiquidAuricular (otic); Ophthalmic
Solution / dropsAuricular (otic); Ophthalmic
Solution / dropsTopical
OintmentAuricular (otic); Ophthalmic
SprayNasal
CreamTopical
OintmentTopical
Prices
Unit descriptionCostUnit
Gramicidin d powder240.0USD g
Neosporin gu irr 40 mg/ml amp23.12USD ml
Neosporin + pain relief cream0.32USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)229 °CNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0039 mg/mLALOGPS
logP4.38ALOGPS
logP5.96ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)11.56ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count16ChemAxon
Hydrogen Donor Count20ChemAxon
Polar Surface Area519.89 Å2ChemAxon
Rotatable Bond Count50ChemAxon
Refractivity492.33 m3·mol-1ChemAxon
Polarizability194.73 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom
Organic compounds
Super Class
Organic Polymers
Class
Polypeptides
Sub Class
Not Available
Direct Parent
Polypeptides
Alternative Parents
Peptides / Leucine and derivatives / Valine and derivatives / N-acyl-alpha amino acids and derivatives / Tryptamines and derivatives / N-formyl-alpha amino acids / Alpha amino acid amides / Alanine and derivatives / 3-alkylindoles / N-acylethanolamines
show 10 more
Substituents
Polypeptide / Alpha peptide / Leucine or derivatives / Valine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-formyl-alpha-amino acid / N-formyl-alpha amino acid or derivatives / Triptan / Alanine or derivatives
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]

Drug created on June 13, 2005 07:24 / Updated on November 05, 2018 17:48