Design, Synthesis, and Antiviral and Fungicidal Activities of 4-Oxo-4-quinolin-1-yl Acylhydrazone Derivatives.

To discover novel antiviral agents, based on the high antiviral activity of (4-oxo-4-quinolin-1-yl)-acetic acid hydrazide (), a series of 4-oxo-4-quinoline acylhydrazone derivatives were designed, synthesized, and first evaluated for their antiviral and fungicidal activities. Most acylhydrazone derivatives exhibited moderate to good antiviral activities in vivo. The inactive, curative, and protective activities of compounds (51.2, 47.6, and 46.3%), (49.6, 43.0, and 45.2% at 500 mg/L), and (47.1, 49.2, and 44.1%) were higher than those of ribavirin (39.2, 38.0, and 40.8%) at 500 mg/L. Molecular docking showed that compound exhibited a stronger affinity to TMV coat protein (TMV-CP) than ribavirin, with a binding energy (-6.89 kcal/mol) slightly lower than that of ribavirin (-6.08 kcal/mol). Microscale thermophoresis showed that compound ( = 0.142 ± 0.060 μM) exhibited a strong binding ability to TMV-CP, superior to that of ribavirin ( = 0.512 ± 0.257 μM). The results of transmission electron microscopy showed that compound hindered the self-assembly and growth of TMV. The antifungal activities of most compounds were moderate at 50 mg/L, among which compounds and exhibited a 72.1 and 76.5% inhibitory rate against , respectively. Meanwhile, compound exhibited a 60% inhibitory rate against at 50 mg/L.