کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10595104 | 981858 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of N-(2,3,5-triazoyl)mycophenolic amide and mycophenolic epoxyketone as novel inhibitors of human IMPDH
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
Syntheses of ten derivatives of mycophenolic acid (MPA) at C-6â² position, and structure-activity relationship study among these derivatives, MPA and mycophenolic hydroxamic acid (MPHA) led to discovery of N-(2,3,5-triazolyl)mycophenolic amide 4, (7â²S) mycophenolic epoxyketone 9 and (7â²R) mycophenolic epoxyketone 10 having potent inhibitory activity against human inosine-5â²-monophosphate dehydrogenase (IMPDH) type I and II as well as antiproliferative activity on human leukemia K562 cells. Compounds 4, 9, and 10 showed induction activity of erythroid differentiation in K562 cells. Inhibitory effects of 4 and 10 against IMPDH were attenuated by supplemental guanosine in K562 cells. In contrast, attenuation effect by supplemental guanosine was not significant in the case of 9. Compound 9 weakly inhibited the enzyme activity of HDAC in the nuclear lysate of K562 cells at 10 μM. These observations suggest that the primary target of 4, 9, and 10 is IMPDH, whereas compound 9 partially inhibits a certain type of HDAC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 18, 15 September 2013, Pages 5140-5144
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 18, 15 September 2013, Pages 5140-5144
نویسندگان
Kazuhiro Sunohara, Shinya Mitsuhashi, Kengo Shigetomi, Makoto Ubukata,