Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3202-5. doi: 10.1016/j.bmcl.2011.04.055. Epub 2011 Apr 20.
Anti-HCV activity of aryl diketoacid (ADK) has been characterized by its two pharmacophoric elements, α,β-diketo acid moiety and substituted aryl ring. In this study, as a part of our ongoing efforts to discover a novel anti-HCV compound mimicking the ADK scaffold, we designed 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives of which the dihydroxychromone moiety as well as the arylmethylaminomethyl substituent (R-PhCH(2)NHCH(2)-) were anticipated in exact match with the pharmacophore model of the ADK. The dihydroxychromone derivatives (3a-3u), thus prepared, showed biological activity in a substituent-dependent fashion, thereby leading to selective anti-HCV effect (EC(50)=2.0-14.0 μM, CC(50) >100 μM) with the substituent groups such as Cl, Br, I, and Me specifically at the 3-position of the aromatic ring.
芳基二酮酸（ADK）的抗 HCV 活性由其两个药效团元素所决定，即α，β-二酮酸部分和取代芳基环。在本研究中，作为我们正在进行的发现新型抗 HCV 化合物的努力的一部分，我们设计了 2-芳甲基氨甲基-5,6-二羟色酮衍生物，其中二羟色酮部分以及芳甲基氨甲基取代基（R-PhCH(2)NHCH(2)-）与 ADK 的药效团模型完全匹配。因此制备的二羟色酮衍生物（3a-3u）表现出依赖取代基的生物活性，从而导致具有选择性的抗 HCV 作用（EC(50)=2.0-14.0 μM，CC(50) >100 μM），其中取代基如 Cl、Br、I 和 Me 特别位于芳环的 3-位。
