Design, Synthesis, and Biological Evaluation of Novel Acylhydrazone Derivatives as Potent Neuraminidase Inhibitors.
Li M, Cheng LP, Pang W, Zhong ZJ, Guo LL.
Neuraminidase (NA) is an important target for current research on anti-influenza drugs. The acylhydrazone derivatives containing the -CONHN=CH- framework have been shown to have good NA inhibitory activity. In this paper, a series of novel acylhydrazone NA inhibitors (<b>9a</b>-<b>9n</b>) were designed and synthesized, and the inhibitory activities against NA were evaluated <i>in vitro</i>. The NA inhibition results showed that compound <b>9j</b> has the most potent inhibitory activity (IC<sub>50</sub> = 0.6 μM) against NA, which is significantly lower than that of the positive control oseltamivir carboxylic acid (OSC) (IC<sub>50</sub> = 17.00 μM). Molecular docking analysis indicates that the acylhydrazone group plays an important role in compound <b>9j</b>, which can bind well to the residues Arg371 and Arg292 in the S1 subsite of NA. The good potency of <b>9j</b> may be also ascribed to the extending of morpholinyl ring into the 430-cavity. The results of this work may contribute to the development of more potent NA inhibitors to against mutant influenza viruses.