کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1397336 1501137 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors
چکیده انگلیسی


• The influence of adamantyl moiety on the properties of HDAC inhibitors was investigated.
• The derivatives showed a substantial reduction of inhibitory activity toward HDACs 1–11.
• They showed antiproliferative and proapoptotic activity comparable to that of compounds lacking the adamantyl group.
• A selected compound exhibited an appreciable in vivo antitumor activity against HCT116.

To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 79, 22 May 2014, Pages 251–259
نویسندگان
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