JADO Technologies, Tatzberg 47-51, 01307 Dresden, Germany.
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5165-9. doi: 10.1016/j.bmcl.2013.07.015. Epub 2013 Jul 18.
The influenza A virus (IFV) possesses a highly ordered cholesterol-rich lipid envelope. A specific composition and structure of this membrane raft envelope are essential for viral entry into cells and virus budding. Several steroidal amines were investigated for antiviral activity against IFV. Both, a positively charged amino function and the highly hydrophobic (ClogP≥5.9) ring system are required for IC50 values in the low μM range. An amino substituent is preferential to an azacyclic A-ring. We showed that these compounds either disrupt or augment membrane rafts and in some cases inactivate the free virus. Some of the compounds also interfere with virus budding. The antiviral selectivity improved in the series 3-amino, 3-aminomethyl, 3-aminoethyl, or by introducing an OH function in the A-ring. Steroidal amines show a new mode of antiviral action in directly targeting the virus envelope and its biological functions.
甲型流感病毒（IFV）拥有一个高度有序的富含胆固醇的脂质包膜。这种膜筏包膜的特定组成和结构对于病毒进入细胞和病毒出芽至关重要。几种甾体胺类化合物因其抗 IFV 的抗病毒活性而被研究。正电荷的氨基功能和高疏水性（ClogP≥5.9）的环系都是 IC50 值在低μM 范围内所必需的。氨基取代基优于氮杂环 A 环。我们表明，这些化合物要么破坏要么增加膜筏，在某些情况下还使游离病毒失活。一些化合物还干扰病毒出芽。该系列化合物的抗病毒选择性通过 3-氨基、3-氨甲基、3-乙氨基或在 A 环中引入 OH 功能得到提高。甾体胺类化合物通过直接靶向病毒包膜及其生物学功能，显示出一种新的抗病毒作用模式。
