First Discovery and Stucture-Activity Relationship Study of Phenanthroquinolizidines as Novel Antiviral Agents against <em>Tobacco Mosaic Virus</em> (TMV)

Abstract

<div><p>A series of phenanthroquinolizidine alkaloids <b>1</b>–<b>24</b> were prepared and first evaluated for their antiviral activity against <em>tobacco mosaic virus</em> (TMV). The bioassay results showed that most of these compounds exhibited good to excellent <em>in vivo</em> anti-TMV activity, of which compounds <b>1</b>, <b>2</b>, <b>15</b> and <b>16</b> displayed significantly higher activity than (<em>R</em>)-antofine and commercial Ningnanmycin at the same test condition. The substituents on the phenanthrene moiety play an important role for maintaining high <em>in vivo</em> antiviral activity. The introduction of 6-hydroxyl, which is proposed to interact with TMV RNA, did increased anti-TMV activity. The 14a<em>R</em>-configuration was confirmed to be the preferred antiviral configuration for phenanthroquinolizidine alkaloids. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052933#s1">Introduction</a> of hydroxy group at 15-position of phenanthroquinolizidine alkaloids increased activity for <em>S</em>-configuration but decreased activity for <em>R</em>-configuration. Present study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.</p> </div