Design, synthesis, and antiviral, fungicidal, and insecticidal activities of tetrahydro-β-carboline-3-carbohydrazide derivatives.

According to our previous research on the antiviral activity of β-carboline and tetrahydro-β-carboline derivatives, using (1S,3S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carbohydrazide (1) as a lead compound, series of novel tetrahydro-β-carboline derivatives containing acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. Most of these compounds exhibited excellent antiviral activity both in vitro and in vivo. The in vivo inactivation, curative, and protection activities of compounds 8, 9, 12, 16, 28, 29, and 30 were much higher than that of ribavirin (37.6%, 39.4%, and 37.9% at 500 μg/mL) and the lead compound (40.0%, 42.3%, and 39.6% at 500 μg/mL). Especially, the in vitro and in vivo activities of compound 16 (36.9%, 33.6%, 30.2%, and 35.8%) at 100 μg/mL, which were very close to that of ribavirin (40.0% for in vitro activity) at 500 μg/mL. Compounds 9 and 29 were chosen for the field trials of antiviral efficacy against TMV (tobacco mosaic virus); the results exhibited that both compounds, especially compound 29, showed better activities than control plant virus inhibitors. At the same time, the fungicidal results showed that compounds 6, 9, and 11 exhibited good fungicidal activities against 14 kinds of phytopathogens. Additionally, compounds 3 and 23 exhibited moderate insecticidal activity against the four tested species of insects.