کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394350 1501154 2013 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation
چکیده انگلیسی

Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity.

Figure optionsDownload as PowerPoint slideHighlights
► Aggrecanases are responsible for aggrecan degradation in osteoarthritis.
► A series of arylsulfonamide hydroxamates was synthesized as aggrecanase inhibitors.
► Derivative 18 displayed nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13.
► 18 proved to block ex vivo cartilage degradation without affecting cell viability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 62, April 2013, Pages 379–394
نویسندگان
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