QSAR, in silico docking and in vitro evaluation of chalcone derivatives as potential inhibitors for H1N1 virus neuraminidase

Abstract

Thirty three chalcones were synthesized and tested on viral H1N1 neuraminidase activity by using MUNANA assay [2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid] assay with DANA (2,3-didehydro-2-deoxy-N-acetylneuraminic acid) was used as standard. 2D and 3D-quantitative structure−activity relationship models have been successfully developed with a good correlative and predictive ability for quantitative structure−activity relationships of these chalcone derivatives. Result from the 2D-quantitative structure−activity relationship model indicates that electrostatic parameter enhanced bioactivity of the chalcones while steric substituents diminished their potency as H1N1 neuraminidase inhibitors. 3D-quantitative structure−activity relationship model showed the importance of the position of the hydroxyl group in chalcone derivatives which can influence on hydrophobicity, hydrogen bond donor and aromatic ring features that enhance the biological activity. Finally, docking studies showed that chalcones MC8 and MC16 with low C docker interaction energies and higher numbers of hydrogen bonding have better inhibitory activity against viral H1N1 neuraminidase. © 2016, Springer Science+Business Media New York.