Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors
| العنوان: | Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors |
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| المؤلفون: | Pei-Tzu Huang, Sirle Saul, Shirit Einav, Christopher R. M. Asquith |
| المصدر: | Molecules; Volume 26; Issue 23; Pages: 7338 Molecules Molecules, Vol 26, Iss 7338, p 7338 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | dengue virus (DENV), viruses, Pharmaceutical Science, Virus Replication, Antiviral Agents, Article, Cell Line, Analytical Chemistry, Dengue, Encephalitis Virus, Venezuelan Equine, QD241-441, antivirals, flavivirus, VEEV, Drug Discovery, alphavirus, Animals, Humans, Physical and Theoretical Chemistry, Organic Chemistry, Encephalomyelitis, Venezuelan Equine, Dengue Virus, 4-anilinoquinoline, emerging viruses, Chemistry (miscellaneous), Quinolines, Molecular Medicine |
| الوصف: | Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (12), 6-bromo-N-(5-fluoro-1H-indazol-6-yl)quinolin-4-amine (50) and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (52), with EC50 values of 0.63–0.69 µM for DENV infection. These compound libraries demonstrated very limited toxicity with CC50 values greater than 10 µM in almost all cases. Additionally, the lead compounds were screened for activity against VEEV and demonstrated activity in the low single-digit micromolar range, with 50 and 52 demonstrating EC50s of 2.3 µM and 3.6 µM, respectively. The promising results presented here highlight the potential to further refine this series in order to develop a clinical compound against DENV, VEEV, and potentially other emerging viral threats. |
| وصف الملف: | application/pdf |
| تدمد: | 1420-3049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85a56d2cc444845934fc608ebcc88639Test https://doi.org/10.3390/molecules26237338Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....85a56d2cc444845934fc608ebcc88639 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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