title: First discovery and stucture-activity relationship study of phenanthroquinolizidines as novel antiviral agents against tobacco mosaic virus (TMV).
abstract: A series of phenanthroquinolizidine alkaloids 1-24 were prepared and first evaluated for their antiviral activity against tobacco mosaic virus (TMV). The bioassay results showed that most of these compounds exhibited good to excellent in vivo anti-TMV activity, of which compounds 1, 2, 15 and 16 displayed significantly higher activity than (R)-antofine and commercial Ningnanmycin at the same test condition. The substituents on the phenanthrene moiety play an important role for maintaining high in vivo antiviral activity. The introduction of 6-hydroxyl, which is proposed to interact with TMV RNA, did increased anti-TMV activity. The 14aR-configuration was confirmed to be the preferred antiviral configuration for phenanthroquinolizidine alkaloids. Introduction of hydroxy group at 15-position of phenanthroquinolizidine alkaloids increased activity for S-configuration but decreased activity for R-configuration. Present study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Anzheng
authors.initials: A
authors.lastname: Feng
authors.forename: Mingbo
authors.initials: M
authors.lastname: Cui
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods; D008954:Models, Biological; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014026:Nicotiana / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D014027:Tobacco Mosaic Virus / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D010618:Phenanthrolines; D011807:Quinolizines; C521641:phenanthroquinolizidine