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Structure-Based Design of 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor as a Potential Herbicide for Cotton Fields
- Source :
- Journal of Agricultural and Food Chemistry; April 2023, Vol. 71 Issue: 14 p5783-5795, 13p
- Publication Year :
- 2023
-
Abstract
- 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most promising herbicide targets for the development of agricultural chemicals owing to its unique mechanism of action in plants. We previously reported on the co-crystal structure of Arabidopsis thaliana(At) HPPD complexed with methylbenquitrione (MBQ), an inhibitor of HPPD that we previously discovered. Based on this crystal structure, and in an attempt to discover even more effective HPPD-inhibiting herbicides, we designed a family of triketone-quinazoline-2,4-dione derivatives featuring a phenylalkyl group through increasing the interaction between the substituent at the R1position and the amino acid residues at the active site entrance of AtHPPD. Among the derivatives, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(1-phenylethyl)quinazoline-2,4(1H,3H)-dione (23) was identified as a promising compound. The co-crystal structure of compound 23with AtHPPD revealed that hydrophobic interactions with Phe392 and Met335, and effective blocking of the conformational deflection of Gln293, as compared with that of the lead compound MBQ, afforded a molecular basis for structural modification. 3-(1-(3-Fluorophenyl)ethyl)-6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione (31) was confirmed to be the best subnanomolar-range AtHPPD inhibitor (IC50= 39 nM), making it approximately seven times more potent than MBQ. In addition, the greenhouse experiment showed favorable herbicidal potency for compound 23with a broad spectrum and acceptable crop selectivity against cotton at the dosage of 30–120 g ai/ha. Thus, compound 23possessed a promising prospect as a novel HPPD-inhibiting herbicide candidate for cotton fields.
Details
- Language :
- English
- ISSN :
- 00218561 and 15205118
- Volume :
- 71
- Issue :
- 14
- Database :
- Supplemental Index
- Journal :
- Journal of Agricultural and Food Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs62646504
- Full Text :
- https://doi.org/10.1021/acs.jafc.2c08448