4'-HYDROXY-3-METHOXYFLAVONES WITH POTENT ANTIPICORNAVIRUS ACTIVITY
4'-HYDROXY-3-METHOXYFLAVONES WITH POTENT ANTIPICORNAVIRUS ACTIVITY
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DOI：
10.1021/jm00106a039
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发表时间：
1991-02-01
影响因子：
7.3
通讯作者：
VLIETINCK, AJ
中科院分区：
文献类型：
--
作者：
DEMEYER, N;HAEMERS, A;VLIETINCK, AJ
4 '-羟基-3-甲氧基黄酮是一种天然化合物，已知具有抗小核糖核酸病毒如脊髓灰质炎和鼻病毒的抗病毒活性。 为了建立构效关系，合成了一系列类似物，并将其抗病毒活性和细胞毒性与天然来源的黄酮进行了比较。 4 '-羟基和3-甲氧基、5位取代和多取代的A环似乎是高活性的基本要求。 最令人感兴趣的化合物是4 '，7-二羟基-3-甲氧基-5，6-二甲基黄酮，其对脊髓灰质炎病毒1型和鼻病毒15型的体外TI 99值分别> 1000和> 200。 该化合物还对测试的其它鼻病毒血清型（2、9、14、29、39、41、59、63、70、85和89）具有活性，具有0.016至0.5 μ g/mL的MIC 50值。 最后，与槲皮素相反，在艾姆斯试验中，浓度高达2.5 mg时，槲皮素无致突变性。
4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI99 values of > 1000 and > 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC50 values ranging from 0.016 to 0.5-mu-g/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.