کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10591926 | 981769 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2 Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2](/preview/png/10591926.png)
چکیده انگلیسی
A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity. Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0.1-4.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0.1 μM), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72.4 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2°-pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln192(2.95 Ã
), Phe518(2.82Â Ã
) and Arg513(2.63 and 2.73Â Ã
). Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 9, 1 May 2013, Pages 2601-2605
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 9, 1 May 2013, Pages 2601-2605
نویسندگان
Ibrahim A. Al-Suwaidan, Amer M. Alanazi, Adel S. El-Azab, Abdulrahman M. Al-Obaid, Kamal E.H. ElTahir, Azza R. Maarouf, Mohamed A. Abu El-Enin, Alaa A.-M. Abdel-Aziz,