Structural correlates of antibacterial and membrane-permeabilizing activities in acylpolyamines
| Autor: | Rajalakshmi Balakrishna, Stewart J. Wood, Kelly A. Miller, Apurba Datta, E. V. K. Suresh Kumar, Sunil A. David, Thuan B. Nguyen |
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| Rok vydání: | 2006 |
| Předmět: |
Staphylococcus aureus
Cell Membrane Permeability Serum albumin Molecular Conformation Spermine Microbial Sensitivity Tests Hemolysis chemistry.chemical_compound Mice Structure-Activity Relationship Antimicrobial chemotherapy medicine Animals Outbred Strains Escherichia coli Polyamines Toxicity Tests Acute Animals Humans Pharmacology (medical) Mechanisms of Action: Physiological Effects Antibacterial agent Pharmacology biology Dose-Response Relationship Drug Biological activity Human serum albumin Antimicrobial Anti-Bacterial Agents Infectious Diseases Biochemistry chemistry biology.protein Rifampin Antibacterial activity Hydrophobic and Hydrophilic Interactions medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 50(3) |
| ISSN: | 0066-4804 |
| Popis: | A homologous series of mono- and bis-acyl polyamines with varying acyl chain lengths originally synthesized for the purpose of sequestering lipopolysaccharide were evaluated for antimicrobial activity to test the hypothesis that these bis-cationic amphipathic compounds may also bind to and permeabilize intact gram-negative bacterial membranes. Some compounds were found to possess significant antimicrobial activity, mediated via permeabilization of bacterial membranes. Structure-activity relationship studies revealed a strong dependence of the acyl chain length on antimicrobial potency and permeabilization activity. Homologated spermine, bis-acylated with C 8 or C 9 chains, was found to profoundly sensitize Escherichia coli to hydrophobic antibiotics such as rifampin. Nonspecific cytotoxicity is a potential drawback of these membranophilic compounds. However, the surface activity of these cationic amphipaths is strongly attenuated under physiological conditions via binding to serum albumin. Significant antibacterial activity is still retained in the presence of physiological concentrations of human serum albumin, suggesting that these compounds may serve as leads in the development of novel adjuncts to conventional antimicrobial chemotherapy. |
| Databáze: | OpenAIRE |
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