tetano
Editor, Senior Moderator
Eur J Med Chem. 2013 Nov 7;71C:81-90. doi: 10.1016/j.ejmech.2013.10.063. [Epub ahead of print]
Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses.
Barman S, You L, Chen R, Codrea V, Kago G, Edupuganti R, Robertus J, Krug RM, Anslyn EV.
Source
Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
Abstract
A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
Copyright ? 2013 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Carbohydrazide, Hemagglutinin, Influenza, Plaque, Real time PCR
PMID:
24287556
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24287556
Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses.
Barman S, You L, Chen R, Codrea V, Kago G, Edupuganti R, Robertus J, Krug RM, Anslyn EV.
Source
Department of Chemistry, University of Texas at Austin, Austin, TX 78712, USA; Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
Abstract
A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability.
Copyright ? 2013 Elsevier Masson SAS. All rights reserved.
KEYWORDS:
Carbohydrazide, Hemagglutinin, Influenza, Plaque, Real time PCR
PMID:
24287556
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24287556