کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10586015 | 981383 | 2013 | 28 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: 7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors 7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors](/preview/png/10586015.png)
چکیده انگلیسی
A series of 7-substituted sulfocoumarins and 3,4-dihydrosulfocoumarins was obtained by cyclization of the methanesulfonate of 2,4-dihydroxy- or 2-hydroxy-4-methoxybenzaldehyde, followed by derivatization reactions. The new compounds incorporate a range of substituents in position 7 of the heterocyclic ring (hydroxyl, methoxy, carboxylic and alkylsulfonate ester). The compounds were tested for the inhibition of the zinc enzyme human (h) carbonic anhydrase (hCA, EC 4.2.1.1). Unlike the 6-substituted sulfocoumarins which were potent hCA IX and XII inhibitors and ineffective hCA I and II inhibitors, compounds from this series showed low nanomolar hCA II inhibitory properties, and inhibited the mitochondrial isoform hCA VA with KIs in the range of 91-9960Â nM, but were ineffective as hCA I, IX and XII inhibitors. The structure activity relationship for this class of inhibitors was rather clear, with the nature of the 7-substituent strongly influencing hCA VA inhibition, whereas the nature of these groups were less relevant for hCA II inhibition (all reported compounds were highly effective hCA II inhibitors, with KIs in the range of 1.5-8.4Â nM). Since both hCA II and hCA VA are important drug targets (hCA II for antiglaucoma agents; hCA VA for antiobesity drugs), these isoform-selective inhibitors reported here may be considered of interest for various biomedical applications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 15, 1 August 2013, Pages 4502-4510
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 15, 1 August 2013, Pages 4502-4510
نویسندگان
Muhammet Tanc, Fabrizio Carta, Murat Bozdag, Andrea Scozzafava, Claudiu T. Supuran,