title: Synthesis and biological activities of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors.
abstract: 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.
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Yan
authors: Y
authors: Zhang
authors: College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, PR China.
authors: Xing-Hai
authors: XH
authors: Liu
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Yi-Zhou
authors: YZ
authors: Zhan
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Li-Yuan
authors: LY
authors: Zhang
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Zheng-Ming
authors: ZM
authors: Li
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Yong-Hong
authors: YH
authors: Li
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China.
authors: Xiao
authors: X
authors: Zhang
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Enginnering (Tianjin), NanKai University, Tianjian 300071, PR China. Electronic address: nkwbl@nankai.edu.cn.
authors: Bao-Lei
authors: BL
authors: Wang
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D050540:Ketol-Acid Reductoisomerase / Q000037:antagonists & inhibitors*; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008352:Mannich Bases; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole; D050540:Ketol-Acid Reductoisomerase
keywords: 1,3,4-Oxadiazole; Fungicidal activity; Herbicidal activity; Ketol-acid reductoisomerase inhibitors; Mannich base