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Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2013 Aug; Vol. 102 (8), pp. 2450-9. Date of Electronic Publication: 2013 Jul 06. - Publication Year :
- 2013
-
Abstract
- By attaching multiple copies of the influenza M2 ion channel inhibitors amantadine (1) and rimantadine (2) to polymeric chains, we endeavored to recover their potency in inhibiting drug-resistant influenza viruses. Depending on loading densities, as well as the nature of the drug, the polymer, and the spacer arm, polymer-conjugated drugs were up to 30-fold more potent inhibitors of drug-resistant strains than their monomeric parents. In particular, a 20% loading density and a short linker group on the negatively charged poly-l-glutamate resulted in one of the most potent inhibitors for 2's conjugates against drug-resistant influenza strains. Although full recovery of the inhibitory action against drug-resistant strains was not achieved, this study may be a step toward salvaging anti-influenza drugs that are no longer effective.<br /> (Copyright © 2013 Wiley Periodicals, Inc.)
- Subjects :
- Amantadine chemistry
Amantadine pharmacology
Animals
Antiviral Agents chemistry
Antiviral Agents pharmacology
Cell Line
Dogs
Drug Resistance, Viral
Humans
Influenza, Human drug therapy
Orthomyxoviridae Infections drug therapy
Polyglutamic Acid chemistry
Rimantadine chemistry
Rimantadine pharmacology
Amantadine administration & dosage
Antiviral Agents administration & dosage
Drug Carriers chemistry
Influenza A virus drug effects
Polymers chemistry
Rimantadine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 102
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 23832466
- Full Text :
- https://doi.org/10.1002/jps.23644