Antiviral Research ( IF 4.5 ) Pub Date : 2017-08-19 , DOI: 10.1016/j.antiviral.2017.08.008 Jih Ru Hwu , Nitesh K. Gupta , Shwu-Chen Tsay , Wen-Chieh Huang , Irina C. Albulescu , Kristina Kovacikova , Martijn J. van Hemert
There are currently still no approved antiviral drugs to treat or prevent chikungunya virus (CHIKV) infections despite the fact that this arbovirus continues to cause outbreaks in Africa, Asia, and South- and Central-America. Thus 20 new conjugated compounds in the families of bis(benzofuran–1,3-thiazolidin-4-one)s and bis(benzofuran–1,3-thiazinan-4-one)s were designed based on the structural features of suramin. These new compounds were synthesized by chemical methods and their structures were confirmed spectroscopically. In CPE reduction assays, six of these new bis-conjugates inhibited CHIKV replication in Vero E6 cells with EC50 in the range of 1.9–2.7 μM and selectivity index values of ∼75 or higher. These results and compounds provide a starting point for further optimization, design, and synthesis of new antiviral agents for this (re)emerging disease.
中文翻译:
双(苯并呋喃–噻唑烷酮)和双(苯并呋喃–噻唑烷酮)作为基孔肯雅病毒抑制剂
尽管该虫媒病毒继续在非洲,亚洲以及南美和中美洲爆发,但目前仍没有批准的抗病毒药物来治疗或预防基孔肯雅病毒(CHIKV)感染。因此,根据苏拉明的结构特征设计了双(苯并呋喃-1,3-噻唑烷-4-酮)家族和双(苯并呋喃-1,3-噻唑烷-4-酮)家族中的20种新的共轭化合物。这些新化合物是通过化学方法合成的,其结构经光谱确认。在CPE还原测定中,这些新的双结合物中有6个在EC 50抑制Vero E6细胞中CHIKV复制在1.9–2.7μM的范围内,选择性指数值为〜75或更高。这些结果和化合物为进一步优化,设计和合成针对这种(新出现的)疾病的新抗病毒药物提供了起点。