School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, China.
School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003, Jiangsu, China.
Bioorg Med Chem. 2019 Nov 1;27(21):115088. doi: 10.1016/j.bmc.2019.115088. Epub 2019 Sep 5.
Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81 µg mL, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63 µg mL. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1 ng mL, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4 Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
从 9-甲基-1,2,3,4,9,9a-六氢-4aH-吡啶并[2,3-b]吲哚-4a-醇或吲哚-3-乙腈出发，合成了 40 种新型角鲨烯生物碱类似物，产率优异。合成的化合物均进行了乙酰胆碱酯酶抑制活性以及广谱植物病原菌抑制活性测试。生物测定结果表明，大多数测试化合物具有与阳性对照相当或更好的体外生物活性。值得注意的是，化合物 b8 和 b9 对黄萎病菌的活性高于百菌清，MIC 值分别为 62.5 和 7.81 µg/mL。化合物 b3 对蜡状芽孢杆菌的活性更高，MIC 值为 15.63 µg/mL。化合物 c2 和 c11 对乙酰胆碱酯酶表现出较强的抑制活性，MIC 值分别为 0.01 和 0.1 ng/mL。c2 和 c11 与美洲电鳗乙酰胆碱酯酶的分子对接模式分析表明，配体的羟基与 Try121 的酚羟基之间存在中等强度的氢键相互作用，距离约为 2.4 Å。本研究的结果将有助于进一步设计和优化角鲨烯生物碱作为防治植物病害的潜在农用化学品先导化合物。
