Yang Yan, Huang Yuanqiong, Song Hongjian, Liu Yuxiu, Wang Lizhong, Wang Qingmin
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.
Mol Divers. 2016 Nov;20(4):829-835. doi: 10.1007/s11030-016-9669-8. Epub 2016 Apr 18.
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.
为研究稠环大小变化及取代基对β-咔啉生物碱抗病毒活性的影响，设计、合成了四种具有吲哚稠合六至九元环结构的新型β-咔啉生物碱类似物，并对其抑制烟草花叶病毒（TMV）的活性进行了评价。生物测定结果表明，这些类似物大多具有显著的抗TMV活性；尤其是I-14（体外500μg/mL时为54±3%；体内500μg/mL时分别为51±2%、45±2%和42±1%）、II-4（体外500μg/mL时为53±1%；体内500μg/mL时分别为49±2%、57±2%和48±1%）和II-8（体外500μg/mL时为48±1%；体内500μg/mL时分别为53±2%、56±2%和46±1%），它们对TMV的抑制作用比利巴韦林更强（体外500μg/mL时为36±1%；体内500μg/mL时分别为37±2%、41±2%和38±1%）。稠环大小对抗TMV效力有重要影响，这可能归因于构象差异。I-1、I-6、II-8和III的X射线结构显示出不同的构象偏好。最有效的化合物可作为进一步优化抗植物病毒剂的先导化合物。
