Discovery of Indoloazepinone Analogues as Novel Antiviral, Antiphytopathogenic Fungus, and Insecticidal Agents

Aldisine alkaloid has a wide range of biological activities and is also the core skeleton of a variety of natural products, but its poor solubility affects its efficacy. In order to improve its solubility and biological activity, a series of indoloazepinone derivatives containing oxime ether, oxime ester, hydrazone, and ester moieties were designed and synthesized, and their antiviral, fungicidal, and larvicidal activities were evaluated. The solubility of these indoloazepinone derivatives improved in comparison with that of aldisine, and most of these compounds showed good antiviral activities against pepper mild mottle virus (PMMoV), among which the 4-chlorobenzoyl oxime ester derivative 5i showed the highest protection, curative, and inactivation activities in vivo (inhibition rate 61 ± 4.1, 60 ± 5.3, and 74 ± 4.2% at 500 mg/L, respectively), which was comparable to that of ningnanmycin (59 ± 2.2, 58 ± 0.7, and 81 ± 4.8% at 500 mg/L, respectively). Compound 5i (the rat acute oral toxicity test, LD50 > 2000 mg/kg) emerged as a promising candidate for anti-PMMoV drug. Most of these compounds have broad-spectrum fungicidal activities, and 5a and 5f showed selectively fungicidal activities against Phytophthora capsici. In addition, these compounds also showed good larvicidal activities against Plutella xylostella and Culex pipiens pallens.