Design, Synthesis, and Anti-tobacco Mosaic Virus (TMV) Activity of Phenanthroindolizidines and Their Analogues

On the basis of our previous structure–activity relationship (SAR) and antiviral mechanism studies, a series of phenanthroindolizidines and their analogues 3–20 were designed, targeting tobacco mosaic virus (TMV) RNA, synthesized, and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds displayed good anti-TMV activity, and some of them exhibited higher antiviral activity than that of commercial Ningnanmycin (perhaps the most successful registered antiplant viral agent). Especially, (S)-deoxytylophorinine (5) with excellent anti-TMV activity (inactivation activity, 59.8%/500 μg mL–1 and 40.3%/100 μg mL–1; curative activity, 65.1%/500 μg mL–1 and 43.7%/100 μg mL–1; and protection activity, 70.2%/500 μg mL–1 and 51.3%/100 μg mL–1) emerged as a potential inhibitor of the plant virus. Compound 20 exhibited a strong in vivo protection effect against TMV at 100 μg mL–1, which indicated that phenanthroindolizidine analogues with a seven-membered D ring have a new and interesting structural scaffold and have great potential for further development as tobacco protection agents.