tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2013 Jul 18. pii: S0960-894X(13)00860-3. doi: 10.1016/j.bmcl.2013.07.015. [Epub ahead of print]
Evaluation of steroidal amines as lipid raft modulators and potential anti-influenza agents.
Agarwal S, Schroeder C, Schlechtingen G, Braxmeier T, Jennings G, Kn?lker HJ.
Source
JADO Technologies, Tatzberg 47-51, 01307 Dresden, Germany; Department of Chemistry, Technische Universit?t Dresden, Bergstr. 66, 01069 Dresden, Germany.
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.
Copyright ? 2013 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antiviral activity, Influenza, Lipid rafts, Raft modulators, Steroidal amines
PMID:
23916260
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23916260
Evaluation of steroidal amines as lipid raft modulators and potential anti-influenza agents.
Agarwal S, Schroeder C, Schlechtingen G, Braxmeier T, Jennings G, Kn?lker HJ.
Source
JADO Technologies, Tatzberg 47-51, 01307 Dresden, Germany; Department of Chemistry, Technische Universit?t Dresden, Bergstr. 66, 01069 Dresden, Germany.
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.
Copyright ? 2013 Elsevier Ltd. All rights reserved.
KEYWORDS:
Antiviral activity, Influenza, Lipid rafts, Raft modulators, Steroidal amines
PMID:
23916260
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23916260