title: Skeletal modifications of β-carboline alkaloids and their antiviral activity profile.
abstract: To study the effect of the variation of fused ring size and substitution on the antiviral activity of [Formula: see text]-carboline alkaloids, four types of structurally novel [Formula: see text]-carboline alkaloids analogues, with indole-fused six- to nine-membered-rings motifs, were designed, synthesized, and evaluated for the inhibition of tobacco mosaic virus (TMV). Bioassay results indicated that most of these analogues had significant anti-TMV activity; especially I-14 (54 [Formula: see text] 3 % at 500 [Formula: see text]g/mL in vitro; 51 [Formula: see text] 2, 45 [Formula: see text] 2, and 42 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), II-4 (53 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 49 [Formula: see text] 2, 57 [Formula: see text] 2, and 48 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), and II-8 (48 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 53 [Formula: see text] 2 %, 56 [Formula: see text] 2 %, and 46 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), which were more potent vs. TMV than was ribavirin (36 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 37 [Formula: see text] 2, 41 [Formula: see text] 2, and 38 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo). The size of the fused ring has important effects on anti-TMV potency, which may be ascribed to conformational differences. The X-ray structures of I-1, I-6, II-8, and III show differing conformational preferences. The most potent compounds can be used as leads for further optimization as antiphytoviral agents.
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, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
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, China.
authors.forename: Yuanqiong
authors.initials: Y
authors.lastname: Huang
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, China. songhongjian@nankai.edu.cn.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Song
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, China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
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, China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
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, China. wang98h@263.net.
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* / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry*; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014027:Tobacco Mosaic Virus / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D002243:Carbolines; C010262:norharman
keywords: -Carboline alkaloids; Anti-TMV; Structure-activity relationship; Tobacco mosaic virus; X-ray structure