کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1369439 1379505 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors
چکیده انگلیسی

Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is recognized as an attractive therapeutic target in multiple malignancies. In this study, a series of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides were synthesized and biologically evaluated for their potential LSD1 inhibitory effect. Among them, compounds 5a and 5n showed the most potent LSD1 inhibitory activity with IC50 values of 1.4 and 1.7 nM, respectively, which were about 10 times more potent compared with (E)-N-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(morpholinosulf-only) benzohydrazide (J. Med. Chem.2013, 56, 9496–9508; as reference compound). Compounds 5a and 5n also exhibited marked anti-proliferation activities against cancer cell lines that highly expressed LSD1. These results suggest that these optimized compounds might be served as promising LSD1 inhibitors against cancer, which merit further study.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 18, 15 September 2016, Pages 4552–4557
نویسندگان
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