title: Design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the Sindbis virus capsid protein.
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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, The Purdue Cancer Center, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Chinmay
authors.initials: C
authors.lastname: Patkar
authors.forename: Ranjit
authors.initials: R
authors.lastname: Warrier
authors.forename: Richard
authors.initials: R
authors.lastname: Kuhn
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D036022:Capsid Proteins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D006224:Cricetinae; D004146:Dioxanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008958:Models, Molecular; D012845:Sindbis Virus / Q000187:drug effects* / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D004146:Dioxanes