tetano
Editor, Senior Moderator
Pharmaceuticals (Basel)
. 2021 Apr 16;14(4):371.
doi: 10.3390/ph14040371.
Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH [SUB]2[/SUB]-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors
Jiqing Ye[SUP] 1 [/SUP], Lin Lin[SUP] 2 [/SUP], Jinyi Xu[SUP] 3 [/SUP], Paul Kay-Sheung Chan[SUP] 2 4 [/SUP], Xiao Yang[SUP] 2 [/SUP], Cong Ma[SUP] 1 [/SUP]
Affiliations
Abstract
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH[SUB]2[/SUB]-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.
Keywords: 150-cavity; influenza virus; neuraminidase inhibitor; oseltamivir derivatives; pyrazole.
. 2021 Apr 16;14(4):371.
doi: 10.3390/ph14040371.
Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH [SUB]2[/SUB]-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors
Jiqing Ye[SUP] 1 [/SUP], Lin Lin[SUP] 2 [/SUP], Jinyi Xu[SUP] 3 [/SUP], Paul Kay-Sheung Chan[SUP] 2 4 [/SUP], Xiao Yang[SUP] 2 [/SUP], Cong Ma[SUP] 1 [/SUP]
Affiliations
- PMID: 33923858
- DOI: 10.3390/ph14040371
Abstract
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH[SUB]2[/SUB]-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.
Keywords: 150-cavity; influenza virus; neuraminidase inhibitor; oseltamivir derivatives; pyrazole.