Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes

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dc.contributor.authorSarıışık, Ediz
dc.contributor.authorKoçak, Mustafa
dc.contributor.authorKüçük, Baloğlu, Fatma
dc.contributor.authorSevercan, Feride
dc.date.accessioned2021-05-15T12:49:57Z
dc.date.available2021-05-15T12:49:57Z
dc.date.issued2019
dc.departmentTıp Fakültesi, Biyofizik Anabilim Dalıen_US
dc.description.abstractSimvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The FTIR results indicate that the effect of simvastatin on membrane structure and dynamics depends on the type of membrane lipids. In anionic DPPG MLVs, high simvastatin concentrations (12, 18, 24 mol%) change the position of the CH 2 antisymmetric stretching mode to lower wavenumber values, implying an ordering effect. However, in zwitterionic DPPC MLVs, high concentrations of simvastatin disorder systems both in the gel and liquid crystalline phases. Moreover, in DPPG and DPPC MLVs, simvastatin has opposite dual effects on membrane dynamics. The bandwidth of the CH 2 antisymmetric stretching modes increases in DPPG MLVs, implying an increase in the dynamics, whereas it decreases in DPPC MLVs. Simvastatin caused broadening of the phase transition peaks and formation of shoulders on the phase transition peaks in DSC curves, indicating multi-domain formations in the phospholipid membranes. Because physical features of membranes such as lipid order and fluidity may be changed with the bioactivity of drugs, opposing effects of simvastatin on the order and dynamics of neutral and charged phospholipids may be critical to deduce the action mechanism of the drug and estimate drug-membrane interactions. © 2019 Elsevier B.V.en_US
dc.description.sponsorshipTürkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 108T616en_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) as a funding program with project number 108T616 .en_US
dc.identifier.doi10.1016/j.bbamem.2019.01.014
dc.identifier.endpage818en_US
dc.identifier.issn0005-2736
dc.identifier.issue4en_US
dc.identifier.pmid30707888
dc.identifier.scopus2-s2.0-85060960531
dc.identifier.scopusqualityQ1
dc.identifier.startpage810en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbamem.2019.01.014
dc.identifier.urihttps://hdl.handle.net/20.500.12939/1152
dc.identifier.volume1861en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorSevercan, Feride
dc.language.isoen
dc.publisherElsevier B.V.en_US
dc.relation.ispartofBiochimica et Biophysica Acta - Biomembranes
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDPPCen_US
dc.subjectDPPGen_US
dc.subjectDSCen_US
dc.subjectFTIR Spectroscopyen_US
dc.subjectSimvastatinen_US
dc.titleInteraction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes
dc.typeArticle

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