tetano
Editor, Senior Moderator
Bioorg Med Chem. 2010 Apr 8. [Epub ahead of print]
Analogs of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses.
Wen WH, Wang SY, Tsai KC, Cheng YS, Yang AS, Fang JM, Wong CH.
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
Abstract
Unlike the group-2 neuraminidase, the group-1 neuraminidase of influenza virus possesses a flexible loop (the 150-loop) and a cavity (the 150-cavity) adjacent to the active site, and renders a conformational change from the 'open' form to the 'closed' form on binding with substrate (sialo-glycoprotein) or inhibitor (e.g., zanamivir). Zanamivir derivative 8a having an extended (piperazinocarbonyl)propyl substituent at the internal N-position of the guanidino group is designed as a possible inhibitor on the basis of computer docking to the open form of N1 subtype neuraminidase. Indeed, compound 8a exhibits strong neuraminidase inhibition and good anti-influenza activity against H1N1 virus with IC(50)=2.15muM and EC(50)=0.77muM, respectively. This study may provide a clue to future design of better group-1 neuraminidase inhibitors. Copyright ? 2010 Elsevier Ltd. All rights reserved.
PMID: 20452227 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20452227
Analogs of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses.
Wen WH, Wang SY, Tsai KC, Cheng YS, Yang AS, Fang JM, Wong CH.
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
Abstract
Unlike the group-2 neuraminidase, the group-1 neuraminidase of influenza virus possesses a flexible loop (the 150-loop) and a cavity (the 150-cavity) adjacent to the active site, and renders a conformational change from the 'open' form to the 'closed' form on binding with substrate (sialo-glycoprotein) or inhibitor (e.g., zanamivir). Zanamivir derivative 8a having an extended (piperazinocarbonyl)propyl substituent at the internal N-position of the guanidino group is designed as a possible inhibitor on the basis of computer docking to the open form of N1 subtype neuraminidase. Indeed, compound 8a exhibits strong neuraminidase inhibition and good anti-influenza activity against H1N1 virus with IC(50)=2.15muM and EC(50)=0.77muM, respectively. This study may provide a clue to future design of better group-1 neuraminidase inhibitors. Copyright ? 2010 Elsevier Ltd. All rights reserved.
PMID: 20452227 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20452227