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

Autor: Qu RY; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China., Yang JF; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China., Liu YC; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China., Chen Q; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China., Hao GF; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China., Niu CW; State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China., Xi Z; State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China.; Collaborative Innovation Center of Chemical Science and Engineering, Tianjing, 300071, People's Republic of China., Yang GF; Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, 430079, People's Republic of China.; Collaborative Innovation Center of Chemical Science and Engineering, Tianjing, 300071, People's Republic of China.
Jazyk: angličtina
Zdroj: Pest management science [Pest Manag Sci] 2017 Jul; Vol. 73 (7), pp. 1373-1381. Date of Electronic Publication: 2016 Dec 07.
DOI: 10.1002/ps.4460
Abstrakt: 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.
(© 2016 Society of Chemical Industry.)
Databáze: MEDLINE
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