Discovery of Tryptanthrins as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

Abstract

Plant diseases seriously affect the yield and quality of crops and are difficult to control. Tryptanthrin and its derivatives (tryptanthrins) were synthesized and evaluated for their antiviral activities and fungicidal activities. We found that tryptanthrins have good antiviral activities against tobacco mosaic virus (TMV) for the first time. Most of the tryptanthrins showed higher anti-TMV activities than that of ribavirin (inhibitory rates of 40, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities <i>in vivo</i>, respectively). Compound <b>3n</b> (inhibitory rates of 52, 49, and 54% at 500 μg/mL for inactivation, curative, and protection activities <i>in vivo</i>, respectively) and compound <b>14</b> (inhibitory rates of 51, 48, and 53% at 500 μg/mL for inactivation, curative, and protection activities <i>in vivo</i>, respectively) emerged as new antiviral lead compounds with excellent antiviral activities. Compound <b>16</b> was selected for further antiviral mechanism research, which revealed that compound <b>16</b> could inhibit virus assembly by decomposing 20S coat protein (CP) disk. Molecular docking results showed that compounds <b>3n</b> and <b>14</b>, which have higher antiviral activities <i>in vivo</i> than that of compound <b>16</b>, do show stronger interaction with TMV CP. Further fungicidal activity tests showed that tryptanthrins displayed broad-spectrum fungicidal activities, especially for compound <b>16</b>. These compounds showed good selectivity to <i>Physalospora piricola</i>. In the current study, a small molecular library of tryptanthrin was constructed and the bioactivity spectrum of these compounds was broadened, which lays a foundation for their application in plant protection.