Acemetacin-phosphatidylcholine interactions are determined by the drug ionization state

Physical Chemistry Chemical Physics : PCCP
Catarina Pereira-LeiteSalette Reis

Abstract

Gastrointestinal (GI) toxicity is a major drawback of the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAIDs topical actions on the protective phospholipid layers of the GI mucosa seem to be a central toxicity mechanism of these pharmaceuticals. This work describes the interactions of acemetacin, a commercialized NSAID, with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at pH 3.0, 5.0, and 7.4. This pH range was chosen to mimic the pH gradient found in the gastric mucosa, and to ultimately gain insights into the mechanisms underlying the acemetacin-induced gastric toxicity. Various experimental techniques were combined to characterize the partitioning of acemetacin in DMPC bilayers, and its effects on the phase transition behavior, as well as the structure and dynamics of DMPC bilayers. The acemetacin-DMPC interactions were clearly pH-dependent. The neutral (protonated) form of acemetacin had more affinity for the DMPC bilayer than the negatively charged form. Due to the higher affinity of neutral acemetacin, the drug effects on the phase transition and the structure and dynamics of the DMPC bilayer were more pronounced at lower pH values. In general, acemetacin decreased the temperature and ...Continue Reading

References

Dec 15, 1978·Biochimica Et Biophysica Acta·S SchreierI C Smith
Aug 8, 1978·Biochemistry·J Seelig, N Waespe-Sarcevic
Sep 24, 1991·Biochemistry·J Seelig, P Ganz
Jul 17, 1998·Biochimica Et Biophysica Acta·R Koynova, M Caffrey
Nov 10, 1998·Chemistry and Physics of Lipids·H I PetracheJ F Nagle
Dec 24, 2002·Biophysical Journal·Stephanie Tristram-NagleJohn F Nagle
Aug 29, 2003·Biophysical Journal·Mitsuhiro HiraiHiroshi Takahashi
Nov 5, 2003·Journal of Lipid Research·Tomasz RógMarta Pasenkiewicz-Gierula
Mar 14, 2008·Langmuir : the ACS Journal of Surfaces and Colloids·Marlene LúcioGerald Brezesinski
Oct 13, 2009·Biochemistry·Smita P SoniStephen R Wassall
Oct 30, 2010·Nature Protocols·Luís M MagalhãesJosé L F C Lima
May 17, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Michal Markiewicz, Marta Pasenkiewicz-Gierula
May 24, 2011·The Journal of Physical Chemistry. B·Cláudia NunesMarlene Lúcio
Jul 28, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Cláudia NunesMarlene Lúcio
Feb 3, 2012·Journal of the American Chemical Society·Patrícia T MartinsMaria João Moreno
Nov 9, 2012·Journal of the American Chemical Society·Mohan Babu BoggaraRamanan Krishnamoorti
May 25, 2013·Pharmaceutical Research·Cláudia NunesSalette Reis
Dec 7, 2013·Arthritis Research & Therapy·Carlos SostresAngel Lanas
Jan 8, 2014·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Sam HarirforooshFakhreddin Jamali
Jun 10, 2014·Biochimica Et Biophysica Acta·Aboozar Khajeh, Hamid Modarress
Dec 17, 2014·Soft Matter·Kiyotaka Akabori, John F Nagle
Nov 12, 2016·Methods in Molecular Biology·Hongwei Zhang
Dec 23, 2016·Medicinal Research Reviews·Catarina Pereira-LeiteSalette Reis
Jan 7, 2017·Physical Chemistry Chemical Physics : PCCP·V K SharmaM Tyagi
Feb 24, 2017·Physical Chemistry Chemical Physics : PCCP·Adree KhondkerMaikel C Rheinstädter

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Citations

Feb 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Catarina Pereira-LeiteSalette Reis
Jan 2, 2021·Membranes·Catarina Pereira-LeiteSalette Reis
Mar 8, 2021·Journal of Molecular Biology·Carla F SousaPaula Gameiro

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Methods Mentioned

BETA
isothermal titration calorimetry
differential scanning calorimetry
electron
X-ray
light scattering
electron paramagnetic resonance

Software Mentioned

ChemAxon
MarvinSketch
Origin®
SimFonia
Excel® Add - In Solver
ConCat32
Bruker WinEPR

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