Expanding indole diversity: direct 1-step synthesis of 1,2-fused indoles and spiroindolines from 2-halo anilines for fast SAR antiviral elucidation against tobacco mosaic virus (TMV).
To systematically investigate the influence of the variation of the original skeletons and spatial configuration of 2,3-fused indole natural products on antiviral activities, two types of structurally novel and potent pseudo-indole natural product derivatives, 1,2-fused indole and spiroindoline, with different substituents were direct synthesized from 2-halo anilines, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results showed that these compounds exhibited good anti-TMV activity, especially 3f, 3g, 3i, 5e, 5h, and 5l, which were more potent than the commercial anti-virus agent ribavirin. An SAR investigation demonstrates that the original ring size, arrangement, and planarity are not optimal; their anti-TMV activities can be improved by skeleton modification and spatial configuration variation. Both of the structurally novel skeletons provide a new template for antiviral studies, which may also provide some useful information for antiviral mechanism elucidation.
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.
Linwei
L
Chen
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.
Yongxian
Y
Liu
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China. songhongjian@nankai.edu.cn.
Hongjian
H
Song
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.
Yuxiu
Y
Liu
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.
Lizhong
L
Wang
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China. wangqm@nankai.edu.cn.
Qingmin
Q
Wang
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013141:Spiro Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects*
D000814:Aniline Compounds; D000998:Antiviral Agents; D007211:Indoles; D013141:Spiro Compounds
1, 2-Fused indole; Anti-TMV; Pseudo-indole alkaloids; Spiroindoline; Tobacco mosaic virus