title: Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine.
abstract: BACKGROUND
  The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity.
  
  
  RESULTS
  Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine.
  
  
  CONCLUSIONS
  The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents.
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Xiuling
authors: X
authors: Yu
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Peng
authors: P
authors: Wei
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Ziwen
authors: Z
authors: Wang
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Yuxiu
authors: Y
authors: Liu
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Lizhong
authors: L
authors: Wang
authors: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Centre of Chemical Science and Engineering, Nankai University, Tianjin, China.
authors: Qingmin
authors: Q
authors: Wang
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007212:Indolizines / Q000494:pharmacology*; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012254:Ribavirin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D006571:Heterocyclic Compounds; D007211:Indoles; D007212:Indolizines; D010616:Phenanthrenes; D010618:Phenanthrolines; C473343:antofine; C521640:phenanthroindolizidine; C031181:phenanthrene; D012254:Ribavirin
keywords: antiviral activity; heterocycle; mode of action; phenanthrene; tobacco mosaic virus