Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation.
Acetohydroxyacid synthase (AHAS; also known as acetolactate synthase; EC 2.2.1.6, formerly EC 4.1.3.18) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. Weed resistance to AHAS-inhibiting herbicides, increasing at an exponential rate, is becoming a global problem and leading to an urgent demand of developing novel compounds against both resistant and wild AHAS. In the present work, a series of novel 2-aroxyl-1,2,4-triazolopyrimidine derivatives (a total of 55) were designed and synthesized with the aim to discover an antiresistant lead compound. Fortunately, the screening results indicated that many of the newly synthesized compounds showed a better, even excellent, inhibition effect against both the wild-type Arabidopsis thaliana AHAS and P197L mutants. Among them, compounds 5-3 to 5-17, compounds 5-19 to 5-26, compounds 5-28 to 5-45, and compound 5-48 have the lower values of resistance factor (RF) and display a potential power to overcome resistance associated with the P197L mutation in the enzyme levels. Further greenhouse in vivo assay showed that compounds 5-15 and 5-20 displayed "moderate" to "good" herbicidal activity against both the wild type-and the resistant (P197L mutation) Descurainia sophia, even at a rate as low as 0.9375 (g of ai/ha). The above results indicated that these two compounds could be used as new leads for the future development of antiresistance herbicides.
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, PR China.
Yu-Chao
YC
Liu
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, PR China.
Ren-Yu
RY
Qu
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, PR China.
Qiong
Q
Chen
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, PR China.
Jing-Fang
JF
Yang
State Key Laboratory of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, PR China.
Niu
N
Cong-Wei
State Key Laboratory of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, PR China.|Collaborative Innovation Center of Chemical Science and Engineering , Tianjing 30071, PR China.
Xi
X
Zhen
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University , Wuhan 430079, PR China.|State Key Laboratory of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, PR China.|Collaborative Innovation Center of Chemical Science and Engineering , Tianjing 30071, PR China.
Guang-Fu
GF
Yang
D000095:Acetolactate Synthase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017360:Arabidopsis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D019607:Brassicaceae / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D053209:Herbicide Resistance; D006540:Herbicides / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D057685:Plant Weeds / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*; D058728:Weed Control
D004791:Enzyme Inhibitors; D006540:Herbicides; D010940:Plant Proteins; D014227:Triazines; C000606690:azolotriazinone; D000095:Acetolactate Synthase
acetohydroxyacid synthase; herbicide; molecular design; triazolopyrimidines; weed resistance