Bioorganic & Medicinal Chemistry Letters 2005-07-01

Design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the Sindbis virus capsid protein.

Ha Young Kim, Chinmay Patkar, Ranjit Warrier, Richard Kuhn, Mark Cushman

Index: Bioorg. Med. Chem. Lett. 15(13) , 3207-11, (2005)

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Abstract

Dioxane-based antiviral agents targeted to the hydrophobic binding pocket of Sindbis virus capsid protein were designed by computer graphics molecular modeling and synthesized. Virus production using SIN-IRES-Luc and capsid assembly were monitored to evaluate antiviral activity. A compound with a three-carbon linker chain connecting two dioxane moieties inhibited virus production by 50% at a concentration of 40 microM, while (R)-hydroxymethyldioxane inhibited virus production by 50% at a concentration of 1 microM. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1mM.