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.