Marine-Natural-Product Development: First Discovery of Nortopsentin Alkaloids as Novel Antiviral, Anti-phytopathogenic-Fungus, and Insecticidal Agents

Abstract

Nortopsentin alkaloids were found to have potent antiviral, anti-phytopathogenic-fungus, and insecticidal activities for the first time. Antiviral-activity tests revealed that these compounds were very sensitive to substituents, so a series of nortopsentin derivatives were designed, synthesized, and systematically evaluated for their antiviral activities against TMV, their fungicidal activities, and their insecticidal activities on the basis of a structural-diversity-derivation strategy. Compounds <b>2e</b> (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 50, 59, and 56%, respectively, at 500 μg/mL) and <b>2k</b> (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 60, 58, and 52%, respectively, at 500 μg/mL), with excellent antiviral activities and good physicochemical properties, emerged as new lead compounds for novel-antiviral-agent development. Further fungicidal-activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds <b>2f</b>, <b>2h</b>, and <b>2j</b> emerged as new lead compounds for antifungal-activity research. Additionally, all the compounds displayed good insecticidal activities against five kinds of insects, including <i>Mythimna separate</i>, <i>Helicoverpa armigera</i>, <i>Ostrinia nubilalis</i>, <i>Plutella xylostella</i>, and <i>Culex pipiens pallens</i>