Transient permeability induced by alkyl derivatives of amphotericin B in lipid membranes

Abstract

Individual ionic channels were shown to be formed in the brain cholesterol containing phospholipid membranes by two-sided addition of the amphotericin B alkyl derivatives. At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to be transient. Existence of different antibiotic assemblies was justified by the kinetic analysis of the membrane conductance decline following the antibiotic washing out. In order to account for the transient characteristics of the induced conductance, it was proposed that the antibiotic oligomers incorporate into the membrane from the aqueous phase, form channels aggregating with cholesterol, and then dissociate in the bilayer into non-active degraded oligomeric or monomeric forms.

Electrochemical Response of Saccharomyces cerevisiae Corresponds to Cell Viability upon Exposure to Dioclea reflexa Seed Extracts and Antifungal Drugs

“…As shown in Figure 6A, cyclic voltammetry measurements of treated cells with drugs were compared to the cells alone. Amp b (blue) treated cells with concentrations ranging from 5 to 30 µg/mL showed elevated anodic responses, indicating ionic leakage from a porous membrane, as previously demonstrated [24,25]. Similar treatment with Flu (purple) showed no dramatic changes in anodic peak current in the presence of the drug, and this observation was the same when the cells were treated with Rif (green) after eight hours of drug exposure, compared to the Amp b current response within the margin of statistical error.…”

“…The extract data was compared to Amp b because the antifungal ability of the drug to cause cell death has been linked to cellular stress and ionic leakage, with numerous electrochemical studies suggesting a correlation between membrane permeability of ions to the drug mechanism of action [24,25]. As shown in Figure 6A, cyclic voltammetry measurements of treated cells with drugs were compared to the cells alone.…”

Theoretical Aspects of Environmental Monitoring to Assess the Environmental Situation

“…Особенность ПА состоит в том, что это единственный в природе класс соединений, образующий в клеточных и модельных мембранах в комплексе со стеринами структурные ионные каналы [5]. Связь между структурой и функцией ПА можно установить на бислойных липидных мембранах (БЛМ).…”

“…Проведен скрининг биологической активности антибиотиков с помощью метода регистрации электрических характеристик БЛМ в режиме фиксации потенциала и тока [5] и установление связи между структурой антибиотиков и их функцией в мембранах.…”

AAA award winners

“…New derivatives were synthesized in our laboratory which are considerably less toxic than AmB, which shows that it is possible to reduce toxicity of the parent molecule by chemical modifications 15–17. Other derivatives of AmB were obtained by other groups specifically to study the mechanism of action of this antibiotic 18–25. All these new derivatives are currently being regarded and studied only as model compounds, and further studies are necessary to design and develop an efficient new drug 16,26–28…”