کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1215328 966972 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of the lipophilic behaviour of some thiazolidinediones: Relationships with PPAR-γ activity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Investigation of the lipophilic behaviour of some thiazolidinediones: Relationships with PPAR-γ activity
چکیده انگلیسی

Various lipophilicity aspects of five well-known PPAR-γ ligands, belonging to the thiazolidinedione (TZD) class, ciglitazone (CSZ), troglitazone (TGZ), netoglitazone (NGZ) and the ampholytic pioglitazone (PGZ) and rosiglitazone (RGZ), have been explored. The compounds were found to be highly lipophilic as assessed by direct octanol–water partitioning experiments and further confirmed by reversed phase HPLC measurements under different conditions. Immobilised artificial membrane (IAM) chromatographic indices were also determined as an alternative expression of lipophilicity. They were found to show less diversity forming two clusters. Experimental log D/log P values were compared to those predicted by three widely used calculation systems. For the two ampholytic TZDs, the lipophilicity and retention/pH profiles were established over a broad pH range and compared to the corresponding calculated profiles. Lipophilicity indices derived under the different conditions were further compared to biological activity, concerning in vitro transactivation (pEC50) and binding affinity (pKi) data, taken from literature. The most active TZD (RGZ) in both transactivation and binding assay proved to be the less lipophilic analogue. An equation relating pEC50 data to experimental log D7.4 or reversed-phase log kw values could be established, while pKi data did not lead to satisfactory correlation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 857, Issue 2, 1 October 2007, Pages 181–187
نویسندگان
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