摘要
为了发现以漆酶作为潜在靶标的农用杀菌剂候选化合物,以天然产物四氢喹啉衍生物4-甲基-N’-(1,2,3,4-四氢喹啉-1-硫代羰基)苯磺酰肼(4bg)为先导,引入活性片段1,2,3,4-四氢异喹啉,设计合成了14个未见文献报道的磺酰肼类和9个酰肼类化合物.目标物结构均经过^(1)H NMR、^(13)C NMR、HRMS确证.离体抑菌活性测试结果表明,2-甲基-N’-(1,2,3,4-四氢异喹啉-2-碳硫酰基)苯磺酰肼(4b)对苹果腐烂病菌(V.mali)和油菜菌核病菌(S.sclerotiorum)均表现出显著的抑菌活性,EC_(50)分别为4.81,1.57μg/mL,优于先导化合物4bg.同时,5-甲基-N’-(1,2,3,4-四氢异喹啉-2-碳硫酰基)吡嗪-2-甲酰肼(5i)对苹果腐烂病菌、油菜菌核病菌、番茄灰霉病菌(B.cinerea)、稻瘟病菌(M.oryzae)、小麦赤霉病菌(F.graminearum)均表现较好的抑菌活性(EC_(50)=12.88~28.65μg/mL).此外,在50μg/m L浓度下,化合物4b和5i表现出一定的漆酶抑制活性(37.07%,35.49%),与阳性对照半胱氨酸(43.10%)相当.通过分子对接的方法分析了化合物4b和5i与漆酶蛋白的结合模式,为化合物进一步改造提供参考.
In order to find agricultural fungicide candidates with lassase as potential target,14 unreported sulfonyl hydrazide and 9 hydrazide derivatives were designed and synthesized by replacing tetrahydroquinoline skeleton of the lead compound 4-methyl-N'-(1,2,3,4-tetrahydroquinoline-1-carbonothioyl)benzenesulfonohydrazide(4bg)with active fragment 1,2,3,4-tetrahydro-isoquinoline.The structures of the target compounds were confirmed by ^(1)H NMR,^(13)C NMR and HRMS.The in vitro bioassay showed that 2-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)benzenesulfonohydrazide(4b)showed excellent fungicidal activity against V.Mali and S.sclerotiorum with EC_(50) values of 4.81 and 1.57μg/mL,respectively,which were better than that of lead compound 4bg.In addition,5-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)pyrazine-2-carbohydrazide(5i)showed good broad-spectrum fungicidal activity against V.Mali,S.sclerotiorum,B.cinerea,M.oryzae and F.graminearum with EC_(50) range of 12.88~28.65μg/mL.Moreover,compounds 4b and 5i exhibited moderate laccase inhibitory activity(37.07%,35.49%),which were similar to that of cysteine(43.10%)at 50μg/mL.Furthermore,the binding modes of compounds 4b and 5i with laccase protein were simulated by molecular docking method,which provided guidance for further modification of compounds.
作者
徐欢
吴鸿飞
张晓鸣
路星星
孙腾达
亓悦
林誉凡
杨新玲
张莉
凌云
Xu Huan;Wu Hongfei;Zhang Xiaoming;Lu Xingxing;Sun Tengda;Qi Yue;Lin Yufan;Yang Xinling;Zhang Li;Ling Yun(Department of Applied Chemistry,College of Science,China Agricultural University,Beijing 100193)
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2023年第2期725-733,共9页
Chinese Journal of Organic Chemistry
基金
国家自然科学基金(Nos.22077137,21472236)资助项目。
关键词
漆酶抑制剂
1
2
3
4-四氢异喹啉
(磺)酰肼类
抑菌活性
分子对接
laccase inhibitor
1,2,3,4-tetrahydroisoquinoline
(sulfonyl)hydrazide
fungicidal activity
molecular docking
