کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10582636 | 981075 | 2012 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of novel isocytosine derivatives as xanthine oxidase inhibitors from a set of virtual screening hits
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کلمات کلیدی
XDHXanthine oxidase - زانتین اکسیدازAUC - AUCIsocytosine - ایزوسیتوزینintraperitoneal - داخل صفاقیDocking - داکتper oral - در طول دهانXanthine dehydrogenase - زانتین دهیدروژنازHit identification - شناسایی آمارPASS - عبورVirtual screening - غربالگری مجازیarea under curve - منطقه تحت منحنیXanthine oxidase inhibitors - مهار کننده های Xanthine oxidaseXanthine oxidase inhibitor - مهارکننده Xanthine oxidaseMolybdopterin - مولیبدوپترین
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In recent years, xanthine oxidase has emerged as an important target not only for gout but also for cardiovascular and metabolic disorders involving hyperuricemia. Contrary to popular belief, recent clinical trials with uricosurics have demonstrated that enhanced excretion of uric acid is, by itself, not adequate to treat hyperuricemia; simultaneous inhibition of production of uric acid by inhibition of xanthine oxidase is also important. Virtual screening of in-house synthetic library followed by in vitro and in vivo testing led to the identification of a novel scaffold for xanthine oxidase inhibition. In vitro activity results corroborated the results from molecular docking studies of the virtual screening hits. The isocytosine scaffold maintains key hydrogen bonding and pi-stacking interactions in the deep end of the xanthine-binding pocket, which anchors it in an appropriate pose to inhibit binding of xanthine and shows promise for further lead optimization using structure-based drug design approach.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 9, 1 May 2012, Pages 2930-2939
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 9, 1 May 2012, Pages 2930-2939
نویسندگان
Chandrika B-Rao, Asha Kulkarni-Almeida, Kamlesh V. Katkar, Smriti Khanna, Usha Ghosh, Ashish Keche, Pranay Shah, Ankita Srivastava, Vaidehi Korde, Kumar V.S. Nemmani, Nitin J. Deshmukh, Amol Dixit, Manoja K. Brahma, Umakant Bahirat, Lalit Doshi,