Mazzei Mauro, Nieddu Erika, Miele Mariangela, Balbi Alessandro, Ferrone Marco, Fermeglia Maurizio, Mazzei Marco T, Pricl Sabrina, La Colla Paolo, Marongiu Fabio, Ibba Cristina, Loddo Roberta
Department of Pharmaceutical Sciences, Viale Benedetto XV, 3, 16132 Genova, Italy.
Bioorg Med Chem. 2008 Mar 1;16(5):2591-605. doi: 10.1016/j.bmc.2007.11.045. Epub 2007 Nov 22.
Some Mannich bases of 7-hydroxycoumarin (2) and their simple derivatives (3 and 4) were prepared and tested against viruses containing single-stranded, positive-sense RNA genomes (ssRNA(+)). This study was directed toward Flaviviridae and, in particular, HCV surrogate viruses (BVDV, YFV). The 7-hydroxy derivatives 2 were generally devoid of activity, but when position 7 was propylated, the resulting 7-propyloxy derivatives 3 were in some cases endowed with an interesting activity against BVDV. The formation of 7-benzoyl derivatives 4 gave compounds generally lacking in activity against Flaviviridae, whereas the appearance of activity against RSV has been observed. Also some unsymmetrical methylene derivatives 5-7 (namely coumarins bridged to chromones or indoles) were found moderately active in antiviral tests. Derivatives 3 were submitted to a molecular modeling study using DNA polymerase of HCV as a target. The good correlation between calculated molecular modeling IC(50) and experimental EC(50) indicates that DNA polymerase is potentially involved in the inhibition of surrogate HCV viruses.
制备了一些7-羟基香豆素（2）的曼尼希碱及其简单衍生物（3和4），并针对含有单链正义RNA基因组（ssRNA(+)）的病毒进行了测试。本研究针对黄病毒科，特别是丙型肝炎病毒替代病毒（牛病毒性腹泻病毒、黄热病病毒）。7-羟基衍生物2通常没有活性，但当7位被丙基化时，所得的7-丙氧基衍生物3在某些情况下对牛病毒性腹泻病毒具有有趣的活性。7-苯甲酰基衍生物4的形成得到的化合物通常对黄病毒科缺乏活性，而观察到对呼吸道合胞病毒有活性。还发现一些不对称亚甲基衍生物5-7（即与色酮或吲哚桥连的香豆素）在抗病毒试验中有中等活性。以丙型肝炎病毒的DNA聚合酶为靶点，对衍生物3进行了分子模拟研究。计算得到的分子模拟IC(50)与实验EC(50)之间的良好相关性表明，DNA聚合酶可能参与了对丙型肝炎病毒替代病毒的抑制作用。
