Boustie J, Stigliani J L, Montanha J, Amoros M, Payard M, Girre L
Laboratoire de Pharmacognosie et Mycologie, Faculté de Pharmacie, Université de Rennes, France.
J Nat Prod. 1998 Apr;61(4):480-4. doi: 10.1021/np970382v.
A series of 18 aporphinoids have been tested in vitro against human poliovirus. The aporphines (+)-glaucine fumarate (1), (+)-N-methyllaurotetanine (4), (+)-isoboldine (7), and (-)-nuciferine, HCl (10) were found to be active with selectivity indices > 14. The nature of the 1, 2-substituents of the isoquinoline moiety appeared to be critical for antipoliovirus activity. An SAR study demonstrated the importance of a methoxyl group at C-2 on the tetrahydroisoquinoline ring for the induction of antipoliovirus activity. Molecular modeling of some compounds in this series revealed the close similarities between the three-dimensional conformational features of the inactive 1,2-substituted derivatives (+)-boldine (6) and (+)-laurolitsine (5) with derivatives containing the 1,2-(methylenedioxy) moiety, which were generally found to be inactive as exemplified by (+)-cassythicine (9).
已对一系列18种阿朴啡类化合物进行了抗人脊髓灰质炎病毒的体外测试。发现阿朴啡类的富马酸（+）-青藤碱（1）、（+）-N-甲基劳罗替丁（4）、（+）-异波尔定（7）和盐酸（-）-荷叶碱（10）具有活性，其选择性指数>14。异喹啉部分1,2-取代基的性质似乎对抗脊髓灰质炎病毒活性至关重要。一项构效关系研究表明，四氢异喹啉环上C-2位的甲氧基对于诱导抗脊髓灰质炎病毒活性很重要。该系列中一些化合物的分子模型显示，无活性的1,2-取代衍生物（+）-波尔定（6）和（+）-月桂利辛（5）与含有1,2-（亚甲二氧基）部分的衍生物的三维构象特征非常相似，通常发现这些衍生物无活性，如（+）-无根藤碱（9）所示。
