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Membrane active phenylalanine conjugated lipophilic norspermidine derivatives with selective antibacterial activity.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2014 Nov 26; Vol. 57 (22), pp. 9409-23. Date of Electronic Publication: 2014 Nov 05. - Publication Year :
- 2014
-
Abstract
- Natural and synthetic membrane active antibacterial agents offer hope as potential solutions to the problem of bacterial resistance as the membrane-active nature imparts low propensity for the development of resistance. In this report norspermidine based antibacterial molecules were developed that displayed excellent antibacterial activity against various wild-type bacteria (Gram-positive and Gram-negative) and drug-resistant bacteria (methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and β-lactam-resistant Klebsiella pneumoniae). In a novel structure-activity relationship study it has been shown how incorporation of an aromatic amino acid drastically improves selective antibacterial activity. Additionally, the effect of stereochemistry on activity, toxicity, and plasma stability has also been studied. These rapidly bactericidal, membrane active antibacterial compounds do not trigger development of resistance in bacteria and hence bear immense potential as therapeutic agents to tackle multidrug resistant bacterial infections.
- Subjects :
- Bacterial Infections drug therapy
Drug Design
Enterococcus faecium
Humans
Kinetics
Klebsiella pneumoniae
Methicillin-Resistant Staphylococcus aureus
Micelles
Molecular Conformation
Phenylalanine chemical synthesis
Plasma drug effects
Plasma microbiology
Serum drug effects
Serum microbiology
Spermidine chemical synthesis
Spermidine chemistry
Tetrazolium Salts chemistry
Thiazoles chemistry
Vancomycin chemistry
beta-Lactams chemistry
Anti-Bacterial Agents chemistry
Drug Resistance, Bacterial
Microbial Sensitivity Tests
Phenylalanine chemistry
Spermidine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 57
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25335118
- Full Text :
- https://doi.org/10.1021/jm5013566