ABSTRACT
Ten pyrazole derivatives were synthesized and evaluated for their ability to inhibit the replication of influenza virions. All the compounds were synthesized in good-to-excellent yield, and the structures were ascertained with the help of (1) H NMR, (13) C NMR, mass, and elemental analysis. Among the tested series, compound 4i was identified as the most potent analog against the H1N1 virus, with IC50 = 5.4 µM, while the rest of the compounds showed mild-to-moderate inhibition of infection. Moreover, these compounds showed excellent inhibitory activity against influenza A neuraminidase (NA), with IC50 values ranging from 2.15 to 7.54 µM, among which compound 4i showed the most prominent inhibition with IC50 = 1.32 µM. To further exemplify the molecular contacts with NA, a molecular docking study of 4i was conducted with the 3D crystal structure of enzyme H5N1-NA in complex. Results showed that target molecules interact in a similar fashion with oseltamivir and zanamivir by creating interatomic contacts with Trp178, Glu227, and Arg371. Moreover, in the toxicity assay with the porcine renal proximal cell line, LLC-PK1, the confocal images showed no appreciable change in morphological character at the highest tested dose.
