کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1392255 1501127 2015 25 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design, synthesis and biological evaluation of biphenylamide derivatives as Hsp90 C-terminal inhibitors
چکیده انگلیسی


• A small library of biphenylamide derivatives was designed and analogs synthesized.
• Compounds were evaluated for anti-proliferative activity against cancer cell lines.
• Hsp90 inhibition was confirmed by Western blot analysis.
• Several analogs showed low nanomolar inhibitory activity.

Modulation of Hsp90 C-terminal function represents a promising therapeutic approach for the treatment of cancer and neurodegenerative diseases. Current drug discovery efforts toward Hsp90 C-terminal inhibition focus on novobiocin, an antibiotic that was transformed into an Hsp90 inhibitor. Based on structural information obtained during the development of novobiocin derivatives and molecular docking studies, scaffolds containing a biphenyl moiety in lieu of the coumarin ring present in novobiocin were identified as new Hsp90 C-terminal inhibitors. Structure–activity relationship studies produced new derivatives that inhibit the proliferation of breast cancer cell lines at nanomolar concentrations, which corresponded directly with Hsp90 inhibition.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 89, 7 January 2015, Pages 442–466
نویسندگان
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