Design, synthesis, antiviral activity, and structure-activity relationships (SARs) of two types of structurally novel phenanthroindo/quinolizidine analogues.
To investigate the influence of the variation of the original skeletons of natural phenanthroindo/quinolizidine alkaloids on antiviral activities, two types of structurally totally novel analogues 7a, 7b, 16a, and 16b were designed, synthesized, and evaluated against tobacco mosaic virus (TMV) for the first time. Bioassay results indicated that all four of the newly designed analogues showed good to excellent antiviral activities, among which analogue 16a dispalyed comparable activity with that of ningnanmycin, perhaps one of the most successful commercial antiviral agents, thus emerging as a potential inhibitor of plant virus and serving as a new lead for further optimization. Further structure-activity relationships are also discussed, demonstrating for the first time that the same changes of the original skeletons of phenanthroindolizidine and phenanthroquinolizidine exihibted totally different antiviral activities results, providing some original and useful information about the preferential conformation for maintaining high activities.
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Bo
B
Su
Fazhong
F
Chen
Lizhong
L
Wang
Qingmin
Q
Wang
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D054836:Indolizidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007212:Indolizines / Q000737:chemistry*; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry*; D010935:Plant Diseases / Q000821:virology; D011807:Quinolizines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects
C000589811:2,3,12,13-tetramethoxy-5,6,8,9,10,10a-hexahydrodibenzo(f,h)pyrrolo(2,1-a)isoquinoline; D000998:Antiviral Agents; D054836:Indolizidines; D007212:Indolizines; D010616:Phenanthrenes; D010618:Phenanthrolines; D011807:Quinolizines; C521640:phenanthroindolizidine; C521641:phenanthroquinolizidine