title: Spatial Configuration and Three-Dimensional Conformation Directed Design, Synthesis, Antiviral Activity, and Structure-Activity Relationships of Phenanthroindolizidine Analogues.
abstract: Our recent investigation on the antiviral activities against tobacco mosaic virus (TMV) of phenanthroindolizidine alkaloid analogues preliminarily revealed that the basic skeleton and substitution pattern at the C13a position of the molecule, which are closely related to the spatial arrangement of the molecule, have great effects on the biological activity. To further study the in-depth influence of spatial configuration and three-dimensional (3D) conformation of the molecules on their anti-TMV activities and related structure-activity relationship (SAR), a series of D-ring opened derivatives 3, 4, 5a-5j, 6, and 7, chiral 13a- and/or 14-substituted phenanthroindolizidine analogues 10-12 and 18-20, and their enantiomers ent-10-ent-12 and ent-18-ent-20 were synthesized and evaluated for their anti-TMV activities. Bioassay results showed that most of the chiral phenanthroindolizidines displayed good to excellent in vivo anti-TMV activity. Among these compounds, ent-11 showed more potent activity than Ningnanmycin (one of the most successful commercial antiviral agents), thus emerging as a potential inhibitor of the plant virus. Further SARs were also discussed for the first time under the chiral scenario, demonstrating that both spatial configuration and 3D conformation of the molecules are crucial for keeping high anti-TMV activity.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D007212:Indolizines / Q000737:chemistry* / Q000494:pharmacology*; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007212:Indolizines; D010618:Phenanthrolines; C521640:phenanthroindolizidine
keywords: anti-TMV; antiviral activity; phenanthroindolizidine alkaloid; structure−activity relationship; tobacco mosaic virus