Yu Xiuling, Wei Peng, Wang Ziwen, Liu Yuxiu, Wang Lizhong, Wang Qingmin
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.
Pest Manag Sci. 2016 Feb;72(2):371-8. doi: 10.1002/ps.4008. Epub 2015 Apr 23.
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.
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.
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.
菲并吲哚里西啶生物碱安托芬及其类似物对烟草花叶病毒（TMV）具有优异的抗病毒活性。为了简化菲并吲哚里西啶生物碱的结构并便于其合成，基于安托芬与TMV RNA的分子间相互作用，设计并合成了一系列含菲的N-杂环化合物（化合物1至33），并对其抗TMV活性进行了系统评价。
这些化合物大多表现出良好至中等的抗TMV活性。最优化合物5、12和21表现出比先导化合物安托芬和市售利巴韦林更高的活性。选择化合物12进行抗TMV抗病毒效果的田间试验，发现其表现出比对照植物病毒抑制剂更好的活性。选择化合物5和12进行作用方式研究。化合物5和12与分离的TMV RNA结合时荧光强度的变化表明，这些小分子也能与TMV RNA结合，但其结合方式与安托芬非常不同。
结合菲和N-杂环的化合物能够保持菲并吲哚里西啶的抗TMV活性，但其作用方式与安托芬不同。本研究为我们寻找更高效的抗植物病毒试剂奠定了良好基础。
