Document Report Card

Basic Information

ID: ALA4184164

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors.

Authors: Wang Z, Cheng LP, Zhang XH, Pang W, Li L, Zhao JL.

Abstract: Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6 μM against NA, while IC50 value for oseltamivir is 61.1 μM. This compound may be further investigated for the treatment of infection by the new type influenza virus.

CiteXplore: 29141777

DOI: 10.1016/j.bmcl.2017.11.003