How does the N-acylation and esterification of amphotericin B molecule affect its interactions with cellular membrane components-the Langmuir monolayer study.
This work presents the results of Langmuir monolayers study of two amphotericin B derivatives obtained by N-acylation (N-acetylamphotericin B, Ac-AmB) and esterification (amphotericin B methyl ester, AME) of the parent AmB molecule. The main objective of present investigations was to examine the strength and nature of interactions of Ac-AmB and AME with natural membrane components as compared to AmB, and verify the monolayer results with biological studies in vitro. Our experiments were based on surface pressure-area measurements of mixed monolayers formed by the investigated antibiotics and sterols/DPPC. The interactions were analyzed with the following dependencies: compression modulus-surface pressure, mean molecular area-composition, excess molecular area-composition and excess free energy-composition plots. It has been found that both Ac-AmB and AME form monolayers of a liquid expanded state and their stability is highest as compared to AmB films. The investigated compounds mix in monolayers with natural membrane components within the whole range of the antibiotic mole fraction. The quantitative analysis of the interactions of the investigated antibiotics with sterols and DPPC as well as sterols/DPPC interactions allow us to verify the monolayer results with biological results. A good correlation between both kinds of studies has been found.
Hac-Wydro
K
K
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
Dynarowicz-Łatka
P
P
Grzybowska
J
J
Borowski
E
E
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000215:Acylation; D000388:Air; D000666:Amphotericin B / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D003102:Colloids / Q000737:chemistry; D004952:Esters; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008566:Membranes / Q000737:chemistry; D008956:Models, Chemical; D015233:Models, Statistical; D011312:Pressure; D011485:Protein Binding; D013261:Sterols / Q000737:chemistry; D013499:Surface Properties; D013816:Thermodynamics; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003102:Colloids; D004952:Esters; D013261:Sterols; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B; D002784:Cholesterol