tetano
Editor, Senior Moderator
ACS Med Chem Lett. 2019 Nov 25;10(12):1667-1673. doi: 10.1021/acsmedchemlett.9b00447. eCollection 2019 Dec 12. [h=1]Discovery of Novel Neuraminidase Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay.[/h]
Yu R[SUP]1[/SUP], Cheng LP[SUP]1[/SUP], Li M[SUP]1[/SUP], Pang W[SUP]1[/SUP].
[h=3]Author information[/h] 1 School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
[h=3]Abstract[/h] Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N'-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC[SUB]50[/SUB] = 0.21 μM) against NA, which is better than oseltamivir carboxylate (OSC) (IC[SUB]50[/SUB] = 3.04 μM) and lead AN-329/10738021 (IC[SUB]50[/SUB] = 1.92 μM). Molecular docking analysis indicates that the good potency of Y-1 may be ascribed to the elongation of the benzylidene moiety of the molecule to the 430-cavity. The results of this study may offer useful reference for development of novel NA inhibitors.
Copyright ? 2019 American Chemical Society.
PMID: 31857844 PMCID: PMC6912870 [Available on 2020-12-12] DOI: 10.1021/acsmedchemlett.9b00447
Yu R[SUP]1[/SUP], Cheng LP[SUP]1[/SUP], Li M[SUP]1[/SUP], Pang W[SUP]1[/SUP].
[h=3]Author information[/h] 1 School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
[h=3]Abstract[/h] Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N'-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC[SUB]50[/SUB] = 0.21 μM) against NA, which is better than oseltamivir carboxylate (OSC) (IC[SUB]50[/SUB] = 3.04 μM) and lead AN-329/10738021 (IC[SUB]50[/SUB] = 1.92 μM). Molecular docking analysis indicates that the good potency of Y-1 may be ascribed to the elongation of the benzylidene moiety of the molecule to the 430-cavity. The results of this study may offer useful reference for development of novel NA inhibitors.
Copyright ? 2019 American Chemical Society.
PMID: 31857844 PMCID: PMC6912870 [Available on 2020-12-12] DOI: 10.1021/acsmedchemlett.9b00447