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Search results for: ERGOSTEROL
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Molecular modelling of amphotericin B-ergosterol primary complex in water
PublicationBadano właściwości pierwotnego kompleksu amfoterycyny B z ergosterolem przy pomocy symulacji dynamiki molekularnej. Otrzymane w wyniku naszych symulacji rezultaty słabo odpowiadają postulowanym przez innych autorów modelom kompleksu antybiotyk-sterol. Z drugiej strony uzyskane geometrie nie są sprzeczne z wynikami eksperymentów biofizycznych dotyczących powstawania kompleksów w wodzie i w środowisku wodno-alkoholowym.
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Molecular modeling of amphotericin B - ergosterol primary complex in water II
PublicationPrezentowane badania dotyczą oddziaływania antybiotyku polienowego anfoterycyny B (AmB) i ergosterolu (ERG) (typowego sterolu błonowego komórek grzybowych) na poziomie molekularnym. W odróżnieniu od badanego poprzednio kompleksu binarnego analizowany obecnie kompleks AnB/ERG/AmB charakteryzuje się zdecydowanie wiekszą stabilnością i wzglednie sztywną, sandwiczową geometrią. Za trwałość i geometrie kompleksu odpowiedzialne są oddziaływania...
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Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels
PublicationBadania polegały na przeprowadzeniu porównawczej dynamiki molekularnej dla dwóch typów kanałów amfoterycyny B. Obie symulacje różniły się rodzajem sterolu (cholesterol lub ergosterol). Na podstawie wyników przeprowadzonych prac ustalono jakie elementy strukturalne badanych kanałów mogą być odpowiedzialne za selektywne działanie amfoterycyny B.
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On the Possibility of the Amphotericin B-Sterol Complex Formation in Cholesterol- and Ergosterol-Containing Lipid Bilayers: A Molecular Dynamics Study
PublicationAmphotericin B (AmB) is a well-known membrane-active antibiotic that has been used to treat systemicfungal infections for more than 45 years. Therapeutic application of AmB is based on the fact that it is moreactive against ergosterol-containing membranes of fungal cells than against mammalian membranes withcholesterol. In this paper, we examine the hypothesis according to which the selectivity of the AmB's membraneaction originates...
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Comparative molecular modelling of biologically active sterols
PublicationMembrane sterols are targets for a clinically important antifungal agent – amphotericin B. The relatively specific antifungal action of the drug is based on a stronger interaction of amphotericin B with fungal ergosterol than with mammalian cholesterol. Conformational space occupied by six sterols has been defined using the molecular dynamics method to establish if the conformational features correspond to the preferential interaction...
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How do sterols determine the antufungal activitiy of amphotericin B? Free energy of binding between the drug and its membrane targets.
PublicationAmphotericin B (AmB) is a well-known polyene antibiotic used to treat systemic fungal infections. It is commonly accepted that the presence of sterols in the membrane is essential for the AmB biological activity, that is, for the formation of transmembrane ion channels. The selective toxicity of AmB for fungal cells is attributed to the fact that it is more potent against fungal cell membranes containing ergosterol than against...
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Quest for the Molecular Basis of Improved Selective Toxicity of All-Trans Isomers of Aromatic Heptaene Macrolide Antifungal Antibiotics
PublicationThree aromatic heptaene macrolide antifungal antibiotics, Candicidin D, Partricin A (Gedamycin) and Partricin B (Vacidin) were subjected to controlled cis-trans to all trans photochemical isomerization. The obtained all-trans isomers demonstrated substantially improved in vitro selective toxicity in the Candida albicans cells: human erythrocytes model. This effect was mainly due to the diminished hemotoxicity. The molecular modeling...
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The Effect of Sterols on Amphotericin B Self-Aggregation in a Lipid Bilayer as Revealed by Free Energy Simulations
PublicationAmphotericin B (AmB) is an effective but toxic antifungal drug, known to increase the permeability of the cell membrane, presumably by assembling into transmembrane pores in a sterol-dependent manner. The aggregation of AmB molecules in a phospholipid bilayer is, thus, crucial for the drug’s activity. To provide an insight into the molecular nature of this process, here, we report an atomistic molecular dynamics simulation study...
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N-(1-Piperidinepropionyl)amphotericin B methyl ester (PAME) - a new derivative of the antifungal antibiotic amphotericin B: Searching for the mechanism of its reduced
PublicationZ zastosowaniem techniki monowarstw Langmuira zbadano naturę oddziaływań pochodnej antybiotyku przeciwgrzybowego amfoterycyny B o obniżonej toksyczności tj. estru metylowego N-(1-piperydynopropionylo)amfoterycyny B (PAME) z komponentami błon biologicznych takich jak: ergosterol, cholesterol i modelowy fosfolipid DPPC i stwierdzono, że zróżnicowanie tych oddziaływań jest podstawą obniżonej toksyczności związku.
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Elicitation strategies for the improvement of essential oil content in Rhododendron tomentosum (Ledum palustre) bioreactor-grown microshoots
PublicationRhododendron tomentosum Harmaja, previously Ledum palustre L., is a fragrant plant growing in swampy areas, which is characterized by well-known repellent properties and the anti-arthritic potential. In the present study, R. tomentosum microshoots cultivated in RITA® bioreactor, providing the alternative, environment-independent source of the valuable essential oil, were treated for 7 days with copper and nickel salts, methyl jasmonate,...
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Mechanism of Binding of Antifungal Antibiotic Amphotericin B to Lipid Membranes: An Insight from Combined Single-Membrane Imaging, Microspectroscopy, and Molecular Dynamics
PublicationAmphotericin B is a lifesaving polyene antibiotic used in the treatment of systemic mycoses. Unfortunately, the pharmacological applicability of this drug is limited because of its severe toxic side effects. At the same time, the lack of a well-defined mechanism of selectivity hampers the efforts to rationally design safer derivatives. As the drug primarily targets the biomembranes of both fungi and humans, new insights into the...
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Membrane Sterols Modulate the Binding Mode of Amphotericin B without Affecting Its Affinity for a Lipid Bilayer
PublicationMembrane-active antibiotics are known to selectively target certain pathogens based on cell membrane properties, such as fluidity, lipid ordering, and phase behavior. These are in turn modulated by the composition of a lipid bilayer and in particular by the presence and type of membrane sterols. Amphotericin B (AmB), the golden standard of antifungal treatment, exhibits higher activity toward ergosterol-rich fungal membranes, which...
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Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives - A molecular dynamics study.
PublicationAmphotericin B (AmB) is an effective but very toxic antifungal antibiotic. In our laboratory a series of AmB derivatives of improved selectivity of action was synthesized and tested. To understand molecular basis of this improvement, comparative conformational studies of amphotericin B and its two more selectivederivatives were carried out in an aqueous solution and in a lipid membrane. These molecular simulation studies revealed...
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Molecular Targets for Anticandidal Chemotherapy
PublicationA relatively small number of anticandidal chemotherapeutics used in clinical practice is at least in part consequence of a limited number of their molecular targets: ergosterol in the membrane, lanosterol demethylase, b(1!3) glucan synthase, and DNA/RNA biosynthesis. Much more potential novel targets have been revealed by the comparative genomic studies identifying essential genes unique for Candida albicans or resulted from recognition...
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Self-assembly, stability and conductance of amphotericin B channels: bridging the gap between structure and function
PublicationAmphotericin B (AmB), one of the most powerful but also toxic drugs used to treat systemic mycoses, is believed to selectively permeabilize fungal cell membranes to ions in a sterol-dependent manner. Unfortunately, the structure of the biologically active AmB channels has long eluded researchers, obstructing the design of safer alternatives. Here, we investigate the structural and thermodynamic aspects of channel formation, stability,...
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Thermodynamics and kinetics of amphotericin B self-association in aqueous solution characterized in molecular detail
PublicationAmphotericin B (AmB) is a potent but toxic drug commonly used to treat systemic mycoses. Its efficiency as a therapeutic agent depends on its ability to discriminate between mammalian and fungal cell membranes. The association of AmB monomers in an aqueous environment plays an important role in drug selectivity, as oligomers formed prior to membrane insertion – presumably dimers – are believed to act differently on fungal (ergosterol-rich)...
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Antibiotic-sterol interactions provide insight into the selectivity of natural aromatic analogues of amphotericin B and their photoisomers
PublicationAromatic heptaene macrolides (AHMs) belong to the group of polyene macrolide antifungal antibiotics. Members of this group were the first to be used in the treatment of systemic fungal infections. Amphotericin B (AmB), a non-aromatic representative of heptaene macrolides, is of significant clinical importance in the treatment of internal mycoses. It includes the all-trans heptaene chromophore, whereas the native AHMs contain two...