Bis(Benzofuran–1,3-N,N-heterocycle)s as Symmetric and Synthetic Drug Leads against Yellow Fever Virus |
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| Authors: | Nitesh K. Gupta Srinivasan Jayakumar Wen-Chieh Huang Pieter Leyssen Johan Neyts Sergey O. Bachurin Jih Ru Hwu Shwu-Chen Tsay |
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| Affiliation: | 1.Department of Chemistry, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 300044, Taiwan;2.Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium;3.The Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russia;4.Department of Chemistry, National Central University, Jhongli City 320317, Taiwan |
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| Abstract: | The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran–1,3-imidazolidin-4-one)s and bis(benzofuran–1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC50 of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases. |
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| Keywords: | yellow fever virus antiviral benzofuran imidazolidinone benzimidazole bis-conjugated compound |
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