Gramicidin D

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

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Gramicidin D (DB00027)

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Synonyms

• Bacillus brevis gramicidin D
• Gramicidin
• Gramicidin A
• Gramicidin B
• Gramicidin C
• Gramicidina
• Gramicidine

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-03-22	Not applicable
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	2009-12-23	Not applicable
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Technilab Pharma Inc.	1998-11-03	2005-08-05
Antibiotic Cream for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Taro Pharmaceuticals, Inc.	2009-07-30	Not applicable
Antibiotic Cream for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	Not applicable	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	2009-12-23	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-04-09	Not applicable
Antibiotic Cream Plus Pain Relief for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-07-11	Not applicable
Antibiotic Drops	Gramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit)	Solution	Auricular (otic); Ophthalmic	Sandoz Canada Incorporated	2017-06-01	Not applicable
Antibiotic Ear Drops	Gramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit)	Solution / drops	Auricular (otic)	Sandoz Canada Incorporated	2017-09-01	Not applicable

International/Other Brands

Sofradex (Sanofi)

Categories

• Amino Acids, Peptides, and Proteins
• Anti-Bacterial Agents
• Anti-Infective Agents
• Anti-Infective Agents, Local
• Membrane Proteins
• P-glycoprotein/ABCB1 Inhibitors
• P-glycoprotein/ABCB1 Substrates
• Peptides
• Peptides, Cyclic
• Pore Forming Cytotoxic Proteins
• Proteins
• Throat Preparations
• Tyrothricin

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

• Superficial Eye Infections

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

• R02AB — Antibiotics
• R02A — THROAT PREPARATIONS
• R02 — THROAT PREPARATIONS
• R — RESPIRATORY SYSTEM

MSDS

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Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Unknown Status	Treatment	Hordeolum	1
Not Available	Completed	Treatment	Nasal Carriers of Staphylococcus Aureus	1
Not Available	Withdrawn	Prevention	Blood Stream Infections / Skin Diseases, Infectious	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

• Johnson & Johnson Healthcare
• Monarch Pharmacy
• Professional Co.

Dosage forms

Form	Route	Strength
Solution / drops	Auricular (otic)
Solution / drops	Ophthalmic
Solution	Ophthalmic
Solution	Auricular (otic); Ophthalmic
Liquid	Ophthalmic
Liquid	Auricular (otic); Ophthalmic
Solution / drops	Auricular (otic); Ophthalmic
Solution / drops	Topical
Ointment	Auricular (otic); Ophthalmic
Spray	Nasal
Cream	Topical
Ointment	Topical

Prices

Unit description	Cost	Unit
Gramicidin d powder	240.0USD	g
Neosporin gu irr 40 mg/ml amp	23.12USD	ml
Neosporin + pain relief cream	0.32USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	229 °C	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0039 mg/mL	ALOGPS
logP	4.38	ALOGPS
logP	5.96	ChemAxon
logS	-5.7	ALOGPS
pKa (Strongest Acidic)	11.56	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	16	ChemAxon
Hydrogen Donor Count	20	ChemAxon
Polar Surface Area	519.89 Å2	ChemAxon
Rotatable Bond Count	50	ChemAxon
Refractivity	492.33 m3·mol-1	ChemAxon
Polarizability	194.73 Å3	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

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-acylethanolaminesSubstituted pyrroles / N-acyl amines / Benzenoids / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds / Carbonyl compounds / Hydrocarbon derivatives / Organic oxides / Primary alcohols

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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 derivativesN-substituted-alpha-amino acid / Alpha-amino acid or derivatives / 3-alkylindole / Indole / Indole or derivatives / N-acylethanolamine / Fatty amide / N-acyl-amine / Fatty acyl / Benzenoid / Substituted pyrrole / Pyrrole / Heteroaromatic compound / Secondary carboxylic acid amide / Carboxamide group / Organoheterocyclic compound / Azacycle / Alkanolamine / Carboxylic acid derivative / Organonitrogen compound / Alcohol / Hydrocarbon derivative / Organic nitrogen compound / Carbonyl group / Organooxygen compound / Organic oxide / Primary alcohol / Organic oxygen compound / Aromatic heteropolycyclic compound

show 29 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

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