Zhang Yan, Liu Xing-Hai, Zhan Yi-Zhou, Zhang Li-Yuan, Li Zheng-Ming, Li Yong-Hong, Zhang Xiao, Wang Bao-Lei
State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, PR China.
Bioorg Med Chem Lett. 2016 Oct 1;26(19):4661-4665. doi: 10.1016/j.bmcl.2016.08.059. Epub 2016 Aug 21.
A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR, (1)H NMR, (13)C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Ki value of (0.96±0.42), (3.86±0.49) and (3.10±0.71) μmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure-activity relationship (SAR) of the active inhibitors in this Letter.
一系列新型的5-取代-1,3,4-恶二唑曼尼希碱和双曼尼希碱已被简便地合成出来，产率良好。它们的结构通过红外光谱、核磁共振氢谱、核磁共振碳谱和元素分析进行了表征。初步生物活性测试结果表明，其中一些化合物对几种受试植物真菌显示出有前景的体外杀菌活性；其中一些对油菜表现出显著的除草活性，并且对水稻酮醇酸还原异构酶（KARI）具有优异的体外抑制活性。在14种新型化合物中，8c、8d和8m表现出较强的KARI抑制活性，其抑制常数（Ki）值分别为(0.96±0.42)、(3.86±0.49)和(3.10±0.71) μmol/L，与异戊烯基羟基肟酸（IpOHA）相当。这些化合物可能是用于进一步研究的新型KARI抑制剂。在本论文中进行了密度泛函理论（DFT）计算和分子对接，以研究活性抑制剂的构效关系（SAR）。
