Neomycin

Neomycin

Systematic (IUPAC) name
(1R,2R,3S,4R,6S)-4,6-diamino-2-
Clinical data
Trade names	Neo-rx
AHFS/Drugs.com	monograph
MedlinePlus	a682274
Pregnancy cat.	?
Legal status	OTC
Routes	Topical, Oral
Pharmacokinetic data
Half-life	2 to 3 hours
Identifiers
CAS number	1404-04-2
ATC code	A01AB08 A07AA01, B05CA09, D06AX04, J01GB05, R02AB01, S01AA03, S02AA07, S03AA01
PubChem	CID 8378
IUPHAR ligand	709
DrugBank	DB00994
ChemSpider	8075
UNII	I16QD7X297 Y
KEGG	D08260
ChEBI	CHEBI:7508
ChEMBL	CHEMBL449118
Chemical data
Formula	C23H46N6O13
Mol. mass	614.644 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C23H46N6O13/c24-2-7-13(32)15(34)10(28)21(37-7)40-18-6(27)1-5(26)12(31)20(18)42-23-17(36)19(9(4-30)39-23)41-22-11(29)16(35)14(33)8(3-25)38-22/h5-23,30-36H,1-4,24-29H2/t5-,6+,7-,8+,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1 Key:PGBHMTALBVVCIT-VCIWKGPPSA-N

Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951. Neomycin, belongs to aminoglycoside class of antibiotics which contain two or more aminosugars connected by glycosidic bonds. Neamine (two rings), Ribostamycin (three rings), Paromomycin (four rings) and Lividomycin (five rings) are some other examples of aminoglycosides. They have shown tremendous potential as antibacterials. One of them, Gentamicin has been used extensively in clinical practice. Due to the inherent oto and nephrotoxicity of these substances, systemic use has declined as safer alternatives have become available.

Uses

Neomycin is overwhelmingly used as a topical preparation, such as Neosporin. It can also be given orally, where it is usually combined with other antibiotics. Neomycin is not absorbed from the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low and prevents hepatic encephalopathy, especially prior to GI surgery. It has also been used to treat small intestinal bacterial overgrowth. It is not given intravenously, as neomycin is extremely nephrotoxic (causes kidney damage), especially compared to other aminoglycosides. The exception is when neomycin is included, in very small quantities, as a preservative in some vaccines - typically 0.025 mg per dose.^[1]

Molecular biology

Neomycin resistance is conferred by either one of two aminoglycoside phosphotransferase genes.^[2] A neo gene is commonly included in DNA plasmids used by molecular biologists to establish stable mammalian cell lines expressing cloned proteins in culture; many commercially available protein expression plasmids contain neo as a selectable marker. Non-transfected cells will eventually die off when the culture is treated with neomycin or similar antibiotic. Neomycin or kanamycin can be used for prokaryotes, but geneticin (G418) is, in general, needed for eukaryotes.

Spectrum

Similar to other aminoglycosides, neomycin has excellent activity against Gram-negative bacteria, and has partial activity against Gram-positive bacteria. It is relatively toxic to humans, and many people have allergic reactions to it.^[3] See: Hypersensitivity. Physicians sometimes recommend using antibiotic ointments without neomycin, such as Polysporin.^[4]

History

Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium Streptomyces fradiae.^[5]

Neomycin as a DNA binder

Neomycin belongs to the family of aminoglycosides. This family includes many other medicinally important drugs: streptomycin, paromomycin and kanamycin . Aminoglycosides are known for their ability to bind to duplex RNA with high affinity. A study done by Daniel Pilch, Associate Professor Dept. of Pharmacology at Rutgers University, and his coworkers determined the association constant for neomycin with A-site RNA was found to be in the ~10⁹ range. However, more than 50 years after its discovery, its DNA-binding properties were still unknown. In 2000, Dev P. Arya, currently Director of the Laboratory of Medicinal Chemistry at Clemson University, and his coworkers discovered that neomycin induces enormous thermal stabilization of triplex DNA while having little or almost no effect on the DNA duplex stabilization. They also showed that neomycin binds to structures that adopt A-form structure, triplex DNA being one of them. They later went on to show that neomycin even induces DNA:RNA hybrid triplex formation. ^[6]

References

1. ^ "Medscape article". http://www.medscape.com/viewarticle/516045_6. 
2. ^ "G418/neomycin-cross resistance?". http://www.bio.net/bionet/mm/methods/1999-March/073912.html. Retrieved 2008-10-19. 
3. ^ DermNet dermatitis/neomycin-allergy
4. ^ "Your Medicine Cabinet". DERMAdoctor.com, Inc.. http://www.dermadoctor.com/article_Your-Medicine-Cabinet_43.html. Retrieved 2008-10-19. 
5. ^ "The Nobel Prize in Physiology or Medicine 1952". Nobel Foundation. http://nobelprize.org/nobel_prizes/medicine/laureates/1952/waksman-bio.html. Retrieved 2008-10-29. 
6. ^ http://www.wiley-vch.de/publish/en/books/bySubjectCH00/ISBN0-471-74302-X/?sID=5vh8aprb95023mtg84ga23gih0