کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2509914 | 1557836 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin-Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1-((5-fluoro-1H-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one (15a) with half-maximal effective concentrations of 17.4-21.1 μM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900 μM. To investigate the structure-activity relationships, two dozens of the hit analogs were synthesized. Among them, 15g, 15j, 15q, 15s, 15t and 15x had anti-influenza viral activity comparable or superior to that of the initial hit. The anti-influenza viral compounds efficiently suppressed not only viral protein level of the infected cells but also production of viral progeny in the culture supernatants in a dose-dependent manner. Based on a mode-of-action study, they did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 107, July 2014, Pages 66-75
Journal: Antiviral Research - Volume 107, July 2014, Pages 66-75
نویسندگان
Ye Jin Jang, Raghavendra Achary, Hye Won Lee, Hyo Jin Lee, Chong-Kyo Lee, Soo Bong Han, Young-Sik Jung, Nam Sook Kang, Pilho Kim, Meehyein Kim,