کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1368531 981701 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rational design and synthesis of novel anti-prostate cancer agents bearing a 3,5-bis-trifluoromethylphenyl moiety
ترجمه فارسی عنوان
طراحی و ترکیب منطقی عوامل جدید ضد سرطان پروستات که حاوی بخش 3،5 بیست تری فلوئورو متیل فنیل هستند
کلمات کلیدی
مدل سازی همگرا، طراحی داروهای روانی، سرطان پروستات، گیرنده آندروژن
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

Prostate cancer is a major cause of male death worldwide and the identification of new and improved treatments is constantly required. Among the available options, different non-steroidal androgen receptor (AR) antagonists are approved also to treat castration-resistant forms. Most of these drugs show limited application due to the development of resistant mutants of their biological target.Following docking-based studies on a homology model for the AR open antagonist conformation, a series of novel 3,5-bis-trifluoromethylphenyl compounds was designed with the aim to improve the antiproliferative activity of anti-androgen drugs bicalutamide and enzalutamide. The new structural modifications might impede the receptor to adopt its closed agonist conformation also in the presence of adaptive mutations.Among the novel compounds synthesised, several displayed significantly improved in vitro activity in comparison with the parent structures, with IC50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145, 22Rv1). Selected hits demonstrated full AR antagonistic behaviour and promising candidates for further development were identified.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 15, 1 August 2016, Pages 3636–3640
نویسندگان
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