Design, synthesis, bioactivity, and DFT calculation of 2-thiazolyl-hydrazone derivatives as influenza neuraminidase inhibitors.

Three series of thiazolylhydrazone derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activity against influenza virus H1N1 in vitro. Compounds 1 and 2 were synthesized via the one-pot reaction and compound 3 was synthesized in two steps. Pharmacological results showed that the majority of the target compounds 1, 2, and 3 exhibited moderate-to-good influenza NA inhibitory activity. The NA inhibitory activity of the most active compound 2g (IC₅₀ = 7.12 μg/ml) is better than that of the lead compound A. Molecular docking was performed to study the possible interactions between compound 2g and the active site of NA. On the basis of biological results, a preliminary structure–activity relationship (SAR) was derived and discussed. Moreover, density functional theory (DFT) calculation was also performed to explain why the thiazolylhydrazone skeleton has NA inhibitory activity, especially compound 2g with the most potent inhibitory activity. [ABSTRACT FROM AUTHOR]