Comparative biophysical studies of sartan class drug molecules losartan and candesartan (CV-11974) with membrane bilayers

Fotakis, C; Christodouleas, D; Zoumpoulakis, P; Kritsi, E; Benetis, N-P; Mavromoustakos, T; Reis, H; Gili, A; Papadopoulos, MG; Zervou, M

dc.contributor.author	Fotakis, C	en
dc.contributor.author	Christodouleas, D	en
dc.contributor.author	Zoumpoulakis, P	en
dc.contributor.author	Kritsi, E	en
dc.contributor.author	Benetis, N-P	en
dc.contributor.author	Mavromoustakos, T	en
dc.contributor.author	Reis, H	en
dc.contributor.author	Gili, A	en
dc.contributor.author	Papadopoulos, MG	en
dc.contributor.author	Zervou, M	en
dc.date.accessioned	2014-03-01T01:35:25Z
dc.date.available	2014-03-01T01:35:25Z
dc.date.issued	2011	en
dc.identifier.issn	1520-6106	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/21041
dc.subject.classification	Chemistry, Physical	en
dc.subject.other	2D-NMR spectroscopy	en
dc.subject.other	Ab initio computations	en
dc.subject.other	Active site	en
dc.subject.other	Alkyl chain	en
dc.subject.other	Bilayer surface	en
dc.subject.other	Biophysical studies	en
dc.subject.other	Candesartan	en
dc.subject.other	Drug molecules	en
dc.subject.other	Dynamic property	en
dc.subject.other	Hydrophobic regions	en
dc.subject.other	Lateral diffusion	en
dc.subject.other	Lipid cores	en
dc.subject.other	Losartan	en
dc.subject.other	Membrane bilayers	en
dc.subject.other	Membrane models	en
dc.subject.other	Mesophases	en
dc.subject.other	Micro-domains	en
dc.subject.other	NMR spectroscopy	en
dc.subject.other	Pharmacological properties	en
dc.subject.other	Polar headgroups	en
dc.subject.other	Polar interactions	en
dc.subject.other	Tetrazoles	en
dc.subject.other	Water interface	en
dc.subject.other	Carbon fiber reinforced plastics	en
dc.subject.other	Drug interactions	en
dc.subject.other	Molecules	en
dc.subject.other	Nuclear magnetic resonance spectroscopy	en
dc.subject.other	Phospholipids	en
dc.subject.other	Lipid bilayers	en
dc.subject.other	angiotensin 1 receptor	en
dc.subject.other	benzimidazole derivative	en
dc.subject.other	candesartan	en
dc.subject.other	losartan	en
dc.subject.other	solvent	en
dc.subject.other	tetrazole derivative	en
dc.subject.other	article	en
dc.subject.other	chemistry	en
dc.subject.other	comparative study	en
dc.subject.other	differential scanning calorimetry	en
dc.subject.other	lipid bilayer	en
dc.subject.other	metabolism	en
dc.subject.other	nuclear magnetic resonance spectroscopy	en
dc.subject.other	Raman spectrometry	en
dc.subject.other	Benzimidazoles	en
dc.subject.other	Calorimetry, Differential Scanning	en
dc.subject.other	Lipid Bilayers	en
dc.subject.other	Losartan	en
dc.subject.other	Magnetic Resonance Spectroscopy	en
dc.subject.other	Receptor, Angiotensin, Type 1	en
dc.subject.other	Solvents	en
dc.subject.other	Spectrum Analysis, Raman	en
dc.subject.other	Tetrazoles	en
dc.title	Comparative biophysical studies of sartan class drug molecules losartan and candesartan (CV-11974) with membrane bilayers	en
heal.type	journalArticle	en
heal.identifier.primary	10.1021/jp110371k	en
heal.identifier.secondary	http://dx.doi.org/10.1021/jp110371k	en
heal.language	English	en
heal.publicationDate	2011	en
heal.abstract	The interactions of the antihypertensive AT1 antagonists candesartan and losartan with membrane bilayers were studied through the application of DSC, Raman, and solid state31P NMR spectroscopies.1H and13C NMR resonances of candesartan were assigned on the basis of 1D and 2D NMR spectroscopy. A31P CP NMR broadline fitting methodology in combination with ab initio computations was implemented and, in conjunction with DSC and Raman results, provided valuable information regarding the perturbation, localization, orientation, and dynamic properties of the drugs in membrane models. In particular, results indicate that losartan anchors in the mesophase region of the lipid bilayers with the tetrazole group oriented toward the polar headgroup, whereas candesartan has less definite localization spanning from water interface toward the mesophase and upper segment of the hydrophobic region. Both sartan molecules decrease the mobilization of the phospholipids alkyl chains. Losartan exerts stronger interactions compared with candesartan, as depicted by the more prominent thermal, structural, and dipolar1H-31P changes that are caused in the lipid bilayers. At higher concentrations, candesartan strengthens the polar interactions and induces increased order at the bilayer surface. At the highest concentration used (20 mol %), only losartan induces formation of microdomains attributed to the flexibility of its alkyl chain. These results in correlation to reported data with other AT1 antagonists strengthen the hypothesis that this class of molecules may approach the active site of the receptor by insertion in the lipid core, followed by lateral diffusion toward the binding site. Further, the similarities and differences of these drugs in their interactions with lipid bilayers establish, at least in part, their pharmacological properties. © 2011 American Chemical Society.	en
heal.publisher	AMER CHEMICAL SOC	en
heal.journalName	Journal of Physical Chemistry B	en
dc.identifier.doi	10.1021/jp110371k	en
dc.identifier.isi	ISI:000290427100052	en
dc.identifier.volume	115	en
dc.identifier.issue	19	en
dc.identifier.spage	6180	en
dc.identifier.epage	6192	en