Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Chemistry, National Central University, Jhongli City 32001, Taiwan.
Department of Chemistry & Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
Antiviral Res. 2015 Jun;118:103-9. doi: 10.1016/j.antiviral.2015.03.013. Epub 2015 Apr 1.
Chikungunya virus (CHIKV) is an arbovirus that was first recognized in an epidemic form in East Africa in 1952-1953. The virus is primarily transmitted through mosquitoes and the resulting disease, chikungunya fever, is found in nearly 40 countries. Neither an effective vaccine nor a specific antiviral drug exists for treatments of chikungunya fever. Thus 22 new conjugated compounds of uracil-coumarin-arene were designed and synthesized as potential inhibiting agents. Their chemical structures were determined unambiguously by spectroscopic methods, including single-crystal X-ray diffraction crystallography. The three units in these conjugates were connected by specially designed -SCH2- and -OSO2- joints. Five of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 10.2-19.1 μM) and showed low toxicity (CC50 = 75.2-178 μM). The selective index values were 8.8-11.5 for three conjugates. By analysis of the data from the anti-viral assays, the structure-activity relationship is derived on the basis of the nature of the uracil, the functional groups attached to the arene, and the joints between the ring units.
基孔肯雅病毒（CHIKV）是一种虫媒病毒，于 1952-1953 年在东非首次以流行形式被发现。该病毒主要通过蚊子传播，由此引发的基孔肯雅热在近 40 个国家流行。目前，针对基孔肯雅热，既没有有效的疫苗，也没有特效的抗病毒药物。因此，我们设计并合成了 22 种新型尿嘧啶-香豆素-芳烃共轭化合物，作为潜在的抑制剂。通过包括单晶 X 射线衍射在内的光谱方法，明确地确定了它们的化学结构。这些共轭物中的三个单元通过专门设计的-SCH2-和-OSO2-接头连接。发现其中 5 种新的共轭物对 Vero 细胞中的 CHIKV 具有显著的抑制作用（EC50=10.2-19.1μM），且毒性较低（CC50=75.2-178μM）。三种共轭物的选择性指数值为 8.8-11.5。通过对抗病毒试验数据的分析，我们得出了基于尿嘧啶的性质、芳环上连接的官能团以及环单元之间的接头的构效关系。
