Discovery of New 2-[(4,6-Dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic Acids as Flexible Inhibitors of Arabidopsis thaliana Acetohydroxyacid Synthase and Its P197L Mutant

• DOI: 10.1021/acs.jafc.7b05198
• Publication Date: 2017-11-30T08:09:53Z
• Authors: Ren-Yu Qu; Jing-Fang Yang; Ponnam Devendar; Wei-Ming Kang; Yu-Chao Liu; Qiong Chen; Cong-Wei Niu; Zhen Xi; Guang-Fu Yang
• Keywords: Arabidopsis Proteins; Herbicides; Arabidopsis; Mutation, Missense; 04 agricultural and veterinary sciences; Benzoates; Molecular Docking Simulation; Acetolactate Synthase; Kinetics; Structure-Activity Relationship; 0401 agriculture, forestry, and fisheries; Enzyme Inhibitors

In the search for new antiresistance acetohydroxyacid synthase (AHAS, EC 2.2.1.6) inhibitors to combat weed resistance associated with AHAS mutations, a series of 2-[(4,6-dimethoxy-1,3,5-triazin-2-yl)oxy]-6-(substituted phenoxy)benzoic acids 11-38 were designed and synthesized via strategy conformational flexibility analysis. Compounds 21, 22, 26, 33, 36, 38 high potency against both wild-type AtAHAS its P197L mutant identified as promising candidates low factors (RF, defined ratio between ki values toward AHAS) ranging from 0.73 6.32. Especially, compound 22 (RF = 0.73) was further most potent inhibitor because significantly reduced level compared that tribenuron-methyl 2650) bispyribac 4.57). Furthermore, compounds also displayed herbicidal activities sensitive resistant (P197L) Descurainia sophia at dosage 75-150 g active ingredient (ai)/ha. Notably, 33 still maintained over 60% activity even much lower dosages (37.5 ai/ha). Therefore, scaffold has great potential discover candidate control mutation.