Serviço de Microbiologia, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, Porto, Portugal.
Bioorg Med Chem. 2010 Jun 15;18(12):4195-201. doi: 10.1016/j.bmc.2010.05.006. Epub 2010 May 7.
Human noroviruses (NoV) are now recognized as the most frequent cause of outbreaks and sporadic cases of acute gastroenteritis. Despite the significant economic impact and considerable morbidity of norovirus disease, no drug or vaccine is currently available to treat or prevent this disease, therefore the discovery of anti-norovirus drugs is urgent. In the present work, a total of 12 structure related chromone and (E)-2-styrylchromones were evaluated for their potential anti-norovirus activity using the murine norovirus (MNV) as a surrogate model for human NoV. From the 12 compounds studied, six (E)-2-styrylchromones were found to have with interesting anti-norovirus activity. The best compounds of the series were (E)-5-hydroxy-2-styrylchromone and (E)-4'-methoxy-2-styrylchromone with an IC(50) approximately 7muM. A first insight into the mechanism of action of these compounds was possible. An interesting relationship between the anti-norovirus activity and the chemical structure was observed. The present study points out that the (E)-2-styrylchromones skeleton is an important one which deserves to be developed and further explored as new antiviral drugs against NoV.
人诺如病毒（NoV）现在被认为是急性肠胃炎暴发和散发的最常见原因。尽管诺如病毒病具有重大的经济影响和相当高的发病率，但目前尚无治疗或预防这种疾病的药物或疫苗，因此，发现抗诺如病毒药物迫在眉睫。在本工作中，使用鼠诺如病毒（MNV）作为人诺如病毒的替代模型，评估了总共 12 种结构相关的色酮和（E）-2-苯乙烯基色酮，以评估其抗诺如病毒活性。在所研究的 12 种化合物中，发现 6 种（E）-2-苯乙烯基色酮具有有趣的抗诺如病毒活性。该系列中最好的化合物是（E）-5-羟基-2-苯乙烯基色酮和（E）-4'-甲氧基-2-苯乙烯基色酮，其 IC50 约为 7μM。对这些化合物的作用机制进行了初步的了解。观察到抗诺如病毒活性与化学结构之间存在有趣的关系。本研究指出，（E）-2-苯乙烯基色酮骨架是一个重要的骨架，值得进一步开发和探索，作为针对 NoV 的新型抗病毒药物。
