Interaction of the macrolide azithromycin with phospholipids. II. Biophysical and computer-aided conformational studies

European Journal of Pharmacology
J P MontenezM P Mingeot-Leclercq

Abstract

In a comparison paper, we show the azithromycin causes a lysosomal phospholipidosis in cultured cells, binds in vitro to negatively charged bilayers without causing aggregation or fusion, and inhibits lysosomal phospholipase A1. In this paper, we show that azithromycin decreases the mobility of the phospholipids in negatively charged liposomes (using 31P nuclear magnetic resonance) and that it increases the fluidity of the acyl chains close to the hydrophilic/hydrophobic interface, but not deeper into the hydrophobic domain (assessed by measuring the fluorescence polarization of trimethylammonium-diphenylhexatriene and diphenyhexatriene, respectively). Computer-aided conformational analysis of mixed monolayers of azithromycin and phosphatidylinositol shows that the drug can be positioned largely in the hydrophobic domain, but close to the interface, with the macrocycle facing the C1 of the fatty acids (allowing the N9a endocyclic tertiary amine to interact with the phospho-groups), the cladinose located on the hydrophobic side of the lipid/water interface and the desosamine projected into the hydrophobic domain. This position is consistent with the experimental data. Analysis of virtual molecules shows that this unanticipated b...Continue Reading

References

Sep 15, 1975·FEBS Letters·A C McLaughlinR E Richards
Jan 1, 1990·The Journal of Antimicrobial Chemotherapy·G FouldsR B Johnson
Jun 1, 1990·Antimicrobial Agents and Chemotherapy·R P Gladue, M E Snider
Sep 1, 1989·Antimicrobial Agents and Chemotherapy·H A Kirst, G D Sides
Apr 1, 1988·AIDS Research and Human Retroviruses·R BrasseurJ M Ruysschaert
Jan 22, 1988·Biochimica Et Biophysica Acta·A V Ferrer-MontielJ A Ferragut
Nov 1, 1987·The Journal of Antimicrobial Chemotherapy·M B CarlierP M Tulkens
Mar 1, 1985·Antimicrobial Agents and Chemotherapy·J R MartinM F Miller
Jan 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·H Träuble, H Eibl
Sep 15, 1974·Biochemical Pharmacology·C de DuveF Van Hoof
May 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R BrasseurJ M Ruysschaert
Nov 16, 1981·Biochemical and Biophysical Research Communications·R BrasseurJ M Ruysschaert
Dec 2, 1980·Biochimica Et Biophysica Acta·E E BurnellB de Kruijff
Apr 28, 1995·European Journal of Pharmacology·F Van BambekeM P Mingeot-Leclercq
Mar 1, 1995·Journal of Toxicology and Environmental Health·M P Mingeot-LeclercqA Schanck
Sep 6, 1994·Chemistry and Physics of Lipids·O G Mouritsen, K Jørgensen
Oct 24, 1996·European Journal of Pharmacology·F Van BambekeM P Mingeot-Leclercq

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Citations

Oct 24, 1996·European Journal of Pharmacology·F Van BambekeM P Mingeot-Leclercq
Feb 22, 2003·Biochimica Et Biophysica Acta·Catarina RodriguesBaltazar de Castro
Nov 16, 2001·Antimicrobial Agents and Chemotherapy·M P Mingeot-LeclercqR Brasseur
Jul 7, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mihailo BanjanacVesna Eraković Haber
Mar 19, 2014·Pharmacology & Therapeutics·Michael J ParnhamRobin Vos
Oct 15, 2013·Journal of Veterinary Pharmacology and Therapeutics·N VillarinoT Martín-Jiménez
Sep 30, 2006·Chemistry and Physics of Lipids·N FaM-P Mingeot-Leclercq
Feb 18, 2015·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·N PrincipiS Esposito
Aug 26, 2004·Biochimica Et Biophysica Acta·A BerquandY F Dufrêne
Dec 13, 2006·Toxicology and Applied Pharmacology·Elizabeth Tengstrand BaronasFrank Y Hsieh
Jun 25, 2009·ChemMedChem·Juha-Matti AlakoskelaPaavo K J Kinnunen
Jun 5, 2014·Future Medicinal Chemistry·Vesna Eraković HaberGoran Kragol
Jul 23, 2009·Journal of Liposome Research·Yimei JiaAbdelwahab Omri
Nov 25, 2004·Clinics in Liver Disease·B A Neuschwander-Tetri
Aug 14, 2001·European Journal of Cell Biology·D TytecaM P Mingeot-Leclercq
May 31, 2018·Journal of Agricultural and Food Chemistry·Ling ChenFang Zhong

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