title: Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of phenanthroindolizidines and their analogues.
abstract: 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.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D054836:Indolizidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007212:Indolizines / Q000737:chemistry*; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D010935:Plant Diseases / Q000821:virology; D012367:RNA, Viral / Q000187:drug effects; D014027:Tobacco Mosaic Virus / Q000187:drug effects* / Q000235:genetics
chemical_list: C569808:(13aS)-deoxytylophorinine; D000998:Antiviral Agents; D054836:Indolizidines; D007212:Indolizines; D010618:Phenanthrolines; D012367:RNA, Viral; C521640:phenanthroindolizidine