کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1356947 | 981177 | 2007 | 13 صفحه PDF | دانلود رایگان |
The crystal structure of the Sindbis virus capsid protein contains one or two solvent-derived dioxane molecules in the hydrophobic binding pocket. A bis-dioxane antiviral agent was designed by linking the two dioxane molecules with a three-carbon chain having R,R connecting stereochemistry, and a stereospecific synthesis was performed. This resulted in an effective antiviral agent that inhibited Sindbis virus replication with an EC50 of 14 μM. The synthesis proceeded through an intermediate (R)-2-hydroxymethyl-[1,4]dioxane, which unexpectedly proved to be a more effecting antiviral agent than the target compound, as evidenced by its EC50 of 3.4 μM as an inhibitor of Sindbis virus replication. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1 mM.
Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 7, 1 April 2007, Pages 2667–2679