tetano
Editor, Senior Moderator
J Med Chem. 2012 Feb 14. [Epub ahead of print]
Design, synthesis and in vitro biological evaluation of 1H-1, 2, 3-triazole-4-carboxamide derivatives as new anti-influenza A agents.
Ding K, Cheng H, Wan J, Liu Y, Lu X, Liu J, Tu Z.
Abstract
The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1, 2, 3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds 3b inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranged from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1) and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-M ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.
PMID:
22332894
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22332894
Design, synthesis and in vitro biological evaluation of 1H-1, 2, 3-triazole-4-carboxamide derivatives as new anti-influenza A agents.
Ding K, Cheng H, Wan J, Liu Y, Lu X, Liu J, Tu Z.
Abstract
The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1, 2, 3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds 3b inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranged from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1) and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-M ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.
PMID:
22332894
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22332894