کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10586334 | 981389 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Structural requirements for inhibitory effects of bisphenols on the activity of the sarco/endoplasmic reticulum calcium ATPase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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![عکس صفحه اول مقاله: Structural requirements for inhibitory effects of bisphenols on the activity of the sarco/endoplasmic reticulum calcium ATPase Structural requirements for inhibitory effects of bisphenols on the activity of the sarco/endoplasmic reticulum calcium ATPase](/preview/png/10586334.png)
چکیده انگلیسی
Bisphenols (BPs) are a class of small organic compounds with widespread industrial applications. Previous studies have identified several BPs that interfere with the activity of the ion-translocating enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). In order to define the molecular determinants of BP-mediated SERCA inhibition, we conducted enzyme activity assays with rabbit SERCA to determine the inhibitory potencies of 27 commercially available BPs, which were the basis for structure-activity relationships. The most potent BPs inhibited SERCA at low micromolar concentrations and carried at their two phenyl rings multiple non-polar substituents, such as small alkyl groups or halides. Furthermore, the presence of methyl groups or a cyclohexyl group at the central carbon atom connecting the two phenyl moieties correlated with good potencies. For a characterization and visualization of enzyme/inhibitor interactions, molecular docking was performed, which suggested that hydrogen bonding with Asp254 and hydrophobic interactions were the major driving forces for BP binding to SERCA. Calcium imaging studies with a selection of BPs showed that these inhibitors were able to increase intracellular calcium levels in living human cells, a behavior consistent with that of a SERCA inhibitor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 13, 1 July 2013, Pages 3927-3933
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 13, 1 July 2013, Pages 3927-3933
نویسندگان
Matthew Woeste, Jeffrey Steller, Emily Hofmann, Taylor Kidd, Rahul Patel, Kevin Connolly, Manori Jayasinghe, Stefan Paula,