Details

Autor(en) / Beteiligte

• Qu, Ren‐Yu
• Yang, Jing‐Fang
• Liu, Yu‐Chao
• Chen, Qiong
• Hao, Ge‐Fei
• Niu, Cong‐Wei
• Xi, Zhen
• Yang, Guang‐Fu

Titel

Computational design of novel inhibitors to overcome weed resistance associated with acetohydroxyacid synthase (AHAS) P197L mutant

Ist Teil von

• Pest management science, 2017-07, Vol.73 (7), p.1373-1381

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGOUND Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first common enzyme in the biosynthetic pathway leading to the branched‐chain amino acids in plants and a wide range of microorganisms. With the long‐term and wide application of AHAS inhibitors, weed resistance is becoming a global problem, which leads to an urgent demand for novel inhibitors to antagonize both wild‐type and resistant AHAS. RESULTS Pyrimidinyl salicylic acid derivatives, as one of the main classes of commercial AHAS herbicides, show potential anti‐resistant bioactivity to wild‐type and P197L mutant. In current work, a series of novel 2‐benzoyloxy‐6‐pyrimidinyl salicylic acid derivatives were designed through fragment‐based drug discovery. Fortunately, the newly synthesized compounds showed good inhibitory activity against both wild‐type and P197L mutant. Some compounds not only had a lower resistance factor value but also showed excellent inhibitory activity against wild‐type AHAS and P197L mutant. Furthermore, greenhouse experiments showed compound 11m displayed almost 100% inhibition against both wild‐type and high‐resistant Descurainia sophia at a dosage of 150 g a.i. ha−1. CONCLUSION The present work indicated that the 2‐benzoyloxy‐6‐pyrimidinyl salicylic acid motif was well worth further optimization. Also, compound 11m could be used as a potential anti‐resistant AHAS herbicide, which requires further research. © 2016 Society of Chemical Industry