Design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the Sindbis virus capsid protein.
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.
Kim
Ha Young
HY
Department of Medicinal Chemistry and Molecular Pharmacology, The Purdue Cancer Center, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
Patkar
Chinmay
C
Warrier
Ranjit
R
Kuhn
Richard
R
Cushman
Mark
M
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
D000998:Antiviral Agents; D036022:Capsid Proteins; D004146:Dioxanes