Ni Wanjun, Li Chaojie, Liu Yuxiu, Song Hongjian, Wang Lizhong, Song Haibin, Wang Qingmin
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, People's Republic of China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, People's Republic of China.
J Agric Food Chem. 2017 Mar 15;65(10):2039-2047. doi: 10.1021/acs.jafc.6b05474. Epub 2017 Mar 1.
For the first time, the botanic source natural product matrine was reported to have more potent inhibitory activity against tobacco mosaic virus (TMV) than the commercial virucide ribavirin. On the basis of the structural diversity modification strategy, a series of matrine derivatives was synthesized and systematically evaluated for their antiviral activity against TMV, fungicidal activity, and insecticidal activity. As a result, compounds 3 (inhibitory rate 67.3%, 69.5%, 63.7%, 63.0% at 500 μg/mL for in vitro activity, inactivation, curative, and protection activities in vivo, respectively), 16 (66.7%, 60.7%, 63.8%, 68.9% at 500 μg/mL), and 32 (74.6%, 76.9%, 72.3%, 75.7% at 500 μg/mL) were found to have much higher anti-TMV activity than ribavirin (40.8%, 37.5%, 38.2%, 37.7% at 500 μg/mL), even exhibiting as well as NK-007 (70.3%, 66.1%, 68.4%, 67.5% at 500 μg/mL), which was an efficient compound created by our group previously. At the same time, it was found that matrine and its derivatives had a broad spectrum fungicidal activity (14 fungi), especially the inhibition of compound 32 against Phytophthora capsici Leonian reached 96.4% at a concentration of 50 μg/mL. What's more, all compounds exhibited very good insecticidal activity to five kinds of insects (including Mythimna Separate, Helicoverpa Armigera, Ostrinia Nubilalis, Plutella xylostella, and Culex Pipiens Pallens); especially, the inhibition rate of C. Pipiens Pallens of compound 22 could still reach 70% at 1 μg/mL.
首次报道植物源天然产物苦参碱对烟草花叶病毒（TMV）具有比市售杀病毒剂利巴韦林更强的抑制活性。基于结构多样性修饰策略，合成了一系列苦参碱衍生物，并对其抗TMV活性、杀菌活性和杀虫活性进行了系统评价。结果发现，化合物3（在500μg/mL时，体外活性、体内钝化、治疗和保护活性的抑制率分别为67.3%、69.5%、63.7%、63.0%）、16（在500μg/mL时为66.7%、60.7%、63.8%、68.9%）和32（在500μg/mL时为74.6%、76.9%、72.3%、75.7%）对TMV的活性远高于利巴韦林（在500μg/mL时为40.8%、37.5%、38.2%、37.7%），甚至与我们团队之前创制的高效化合物NK - 007（在500μg/mL时为70.3%、66.1%、68.4%、67.5%）相当。同时，发现苦参碱及其衍生物具有广谱杀菌活性（针对14种真菌），尤其是化合物32对辣椒疫霉的抑制率在50μg/mL浓度下达到96.4%。此外，所有化合物对五种昆虫（包括粘虫、棉铃虫、玉米螟、小菜蛾和淡色库蚊）均表现出良好的杀虫活性；特别是化合物22对淡色库蚊在1μg/mL时的抑制率仍可达70%。
