Target-Directed Design, Synthesis, Antiviral Activity, and SARs of 9-Substituted Phenanthroindolizidine Alkaloid Derivatives
Chang‐Cun Yan, Jianyang Dong, Yuxiu Liu, Yongqiang Li, Qingmin Wang
Abstract
On the basis of our previous studies on the antiviral mechanism against tobacco mosaic virus (TMV) and structure–activity relationship of phenanthroindolizidine alkaloids, a series of 9-substituted tylophorine derivatives targeting TMV RNA were designed, synthesized, and assessed for their anti-TMV activities. The bioassay results indicated that most of these compounds showed good in vivo anti-TMV activities, and some of them displayed higher activity than that of commercial ribavirin. Especially, the anti-TMV activities of compound 3b, 4, and 6 are 2–3 times higher than that of commercial ribavirin, according to EC50 values. In this work, we have demonstrated an effective way to design new inhibitors against plant virus and developed 9-ethoxy methyl tylophorine (4) with excellent anti-TMV activity (in vitro activity, 70.2%/500 μg/mL and 27.1%/100 μg/mL; inactivation activity, 67.7%/500 μg/mL and 30.5%/100 μg/mL; curative activity, 65.3%/500 μg/mL and 30.8%/100 μg/mL; and protection activity, 65.9%/500 μg/mL and 36.0%/100 μg/mL) as a potential plant viral inhibitor.