title: Evaluation of steroidal amines as lipid raft modulators and potential anti-influenza agents.
abstract: 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.
authors.affiliation: JADO Technologies, Tatzberg 47-51, 01307 Dresden, Germany.
authors.forename: Sameer
authors.initials: S
authors.lastname: Agarwal
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schroeder
authors.forename: Georg
authors.initials: G
authors.lastname: Schlechtingen
authors.forename: Tobias
authors.initials: T
authors.lastname: Braxmeier
authors.forename: Gary
authors.initials: G
authors.lastname: Jennings
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Knölker
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D021962:Membrane Microdomains / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000998:Antiviral Agents
keywords: Antiviral activity; Influenza; Lipid rafts; Raft modulators; Steroidal amines