Pore-forming activity of new conjugate antibiotics based on amphotericin B
Autor: | Evgenia N Olsufyeva, Olga S. Ostroumova, E. E. Bykov, Svetlana S. Efimova, Anna N. Tevyashova |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
030106 microbiology Cell Membranes Lipid Bilayers lcsh:Medicine Mycology Microbiology Biochemistry 03 medical and health sciences chemistry.chemical_compound Antibiotics Microbial Control Amphotericin B Medicine and Health Sciences Vesicles Lipid bilayer lcsh:Science Pharmacology Liposome Antifungals Multidisciplinary Chemistry Antifungal antibiotic Antimicrobials lcsh:R Chemical modification Drugs Biology and Life Sciences Cell Biology Polyene Fluoresceins Combinatorial chemistry Lipids Anti-Bacterial Agents Calcein 030104 developmental biology Membrane Microscopy Fluorescence Liposomes Physical Sciences Phosphatidylcholines Lipid Bilayer lcsh:Q Cellular Structures and Organelles Conjugate Research Article Chemical Elements Hydrogen |
Zdroj: | PLoS ONE, Vol 12, Iss 11, p e0188573 (2017) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | A series of amides of the antifungal antibiotic amphotericin B (AmB) and its conjugates with benzoxaboroles was tested to determine whether they form pores in lipid bilayers and to compare their channel characteristics. The tested derivatives produced pores of larger amplitude and shorter lifetime than those of the parent antibiotic. The pore conductance was related to changes in the partial charge of the hydrogens of the hydroxyl groups in the lactone ring that determined the anion coordination in the channel. Neutralization of one of the polar group charges in the AmB head during chemical modification produced a pronounced effect by diminishing the dwell time of the polyene channel compared to modification of both groups. In this study, compounds that had a modification of one carboxyl or amino group were less effective in initializing phase separation in POPC-membranes compared to derivatives that had modifications of both polar groups as well as the parent antibiotic. The effects were attributed to the restriction of the aggregation process by electrical repulsion between charged derivatives in contrast to neutral compounds. The significant correlation between the ability of derivatives to increase the permeability of model membranes-causing the appearance of single channels in lipid bilayers or inducing calcein leakage from unilamellar vesicles-and the minimal inhibitory concentration indicated that the antifungal effect of the conjugates was due to pore formation in the membranes of target cells. |
Databáze: | OpenAIRE |
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