کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1374862 981927 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open-angle glaucoma
چکیده انگلیسی

Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 23, 1 December 2009, Pages 6565–6570
نویسندگان
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