Journal of Agricultural and Food Chemistry p. 5059 - 5067 (2020)
Update date:2022-08-11
Topics:
Chen, Qiong
Hao, Ge-Fei
He, Bo
Lin, Hong-Yan
Wu, Feng-Xu
Wu, Lei
Yang, Guang-Fu
Yang, Wen-Chao
Yu, Liang-Kun
4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been identified as one of the most significant targets in herbicide discovery for resistant weed control. In a continuing effort to discover potent novel HPPD inhibitors, we adopted a ring-expansion strategy to design a series of novel pyrazole-quinazoline-2,4-dione hybrids based on the previously discovered pyrazole-isoindoline-1,3-dione scaffold. One compound, 3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione (9bj), displayed excellent potency against AtHPPD, with an IC50 value of 84 nM, which is approximately 16-fold more potent than pyrasulfotole (IC50 = 1359 nM) and 2.7-fold more potent than mesotrione (IC50 = 226 nM). Furthermore, the co-crystal structure of the AtHPPD-9bj complex (PDB ID 6LGT) was determined at a resolution of 1.75 ?. Similar to the existing HPPD inhibitors, compound 9bj formed a bidentate chelating interaction with the metal ion and a π-πstacking interaction with Phe381 and Phe424. In contrast, o-chlorophenyl at the N3 position of quinazoline-2,4-dione with a double conformation was surrounded by hydrophobic residues (Met335, Leu368, Leu427, Phe424, Phe392, and Phe381). Remarkably, the greenhouse assay indicated that most compounds displayed excellent herbicidal activity (complete inhibition) against at least one of the tested weeds at the application rate of 150 g of active ingredient (ai)/ha. Most promisingly, compounds 9aj and 9bi not only exhibited prominent weed control effects with a broad spectrum but also showed very good crop safety to cotton, peanuts, and corn at the dose of 150 g of ai/ha.
View MoreLuojiang Chenming Biological Products Co
Contact:+86 15000297032
Address:GROUP NO.4, HE SHENG VILLAGE, PANLONG TOWN,
Binzhou Holly Pharmaceutical Co.,Ltd.
Contact:74517
Address:No.15 Dapu Road,Huangpu District Shanghai,P.R.China
Ji'an Hairui Natural Plant Co. Ltd.
Contact:0796-8105528
Address:Meilin industry park, Qingyuan district Ji'an City, Jiangxi Province
Shandong united-rising pharmaceutical cooperation.,ltd.
Contact:008653187965009
Address:171No., Jing5 Road, Shizhong District, Jinan, China
Xinjiang Zhongtai Chemical Co., Ltd.
Contact:+86-991-8788172
Address:NO.78 XISHAN RD.URUMQI,CHINA
Doi:10.1002/chem.201203833
(2013)Doi:10.1002/zaac.19966220924
(1996)Doi:10.1021/jp0567467
(2006)Doi:10.1039/c9ra10447j
(2020)Doi:10.1021/om990462p
(1999)Doi:10.1002/ejoc.202001160
(2020)