tetano
Editor, Senior Moderator
Arch Pharm (Weinheim). 2016 Jan 21. doi: 10.1002/ardp.201500342. [Epub ahead of print]
[h=1]Discovery of Novel Pyrazole Derivatives as Potent Neuraminidase Inhibitors against Influenza H1N1 Virus.[/h] Meng FJ[SUP]1[/SUP], Sun T[SUP]2[/SUP], Dong WZ[SUP]3[/SUP], Li MH[SUP]1[/SUP], Tuo ZZ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Ten pyrazole derivatives were synthesized and evaluated for their ability to inhibit the replication of influenza virions. All the compounds were synthesized in good-to-excellent yield, and the structures were ascertained with the help of [SUP]1[/SUP] H NMR, [SUP]13[/SUP] C NMR, mass, and elemental analysis. Among the tested series, compound 4i was identified as the most potent analog against the H1N1 virus, with IC[SUB]50[/SUB] = 5.4 ?M, while the rest of the compounds showed mild-to-moderate inhibition of infection. Moreover, these compounds showed excellent inhibitory activity against influenza A neuraminidase (NA), with IC[SUB]50[/SUB] values ranging from 2.15 to 7.54 ?M, among which compound 4i showed the most prominent inhibition with IC[SUB]50[/SUB] = 1.32 ?M. To further exemplify the molecular contacts with NA, a molecular docking study of 4i was conducted with the 3D crystal structure of enzyme H5N1-NA in complex. Results showed that target molecules interact in a similar fashion with oseltamivir and zanamivir by creating interatomic contacts with Trp178, Glu227, and Arg371. Moreover, in the toxicity assay with the porcine renal proximal cell line, LLC-PK1, the confocal images showed no appreciable change in morphological character at the highest tested dose.
? 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] Anti-influenza; Docking; Neuraminidase; Pyrazole; Toxicity
PMID: 26797880 [PubMed - as supplied by publisher]
[h=1]Discovery of Novel Pyrazole Derivatives as Potent Neuraminidase Inhibitors against Influenza H1N1 Virus.[/h] Meng FJ[SUP]1[/SUP], Sun T[SUP]2[/SUP], Dong WZ[SUP]3[/SUP], Li MH[SUP]1[/SUP], Tuo ZZ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Ten pyrazole derivatives were synthesized and evaluated for their ability to inhibit the replication of influenza virions. All the compounds were synthesized in good-to-excellent yield, and the structures were ascertained with the help of [SUP]1[/SUP] H NMR, [SUP]13[/SUP] C NMR, mass, and elemental analysis. Among the tested series, compound 4i was identified as the most potent analog against the H1N1 virus, with IC[SUB]50[/SUB] = 5.4 ?M, while the rest of the compounds showed mild-to-moderate inhibition of infection. Moreover, these compounds showed excellent inhibitory activity against influenza A neuraminidase (NA), with IC[SUB]50[/SUB] values ranging from 2.15 to 7.54 ?M, among which compound 4i showed the most prominent inhibition with IC[SUB]50[/SUB] = 1.32 ?M. To further exemplify the molecular contacts with NA, a molecular docking study of 4i was conducted with the 3D crystal structure of enzyme H5N1-NA in complex. Results showed that target molecules interact in a similar fashion with oseltamivir and zanamivir by creating interatomic contacts with Trp178, Glu227, and Arg371. Moreover, in the toxicity assay with the porcine renal proximal cell line, LLC-PK1, the confocal images showed no appreciable change in morphological character at the highest tested dose.
? 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] Anti-influenza; Docking; Neuraminidase; Pyrazole; Toxicity
PMID: 26797880 [PubMed - as supplied by publisher]