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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 [J Agric Food Chem] 2023 Apr 12; Vol. 71 (14), pp. 5783-5795. Date of Electronic Publication: 2023 Mar 28. - Publication Year :
- 2023
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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 R <superscript>1</superscript> position and the amino acid residues at the active site entrance of At HPPD. 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 23 with At HPPD 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 At HPPD inhibitor (IC <subscript>50</subscript> = 39 nM), making it approximately seven times more potent than MBQ . In addition, the greenhouse experiment showed favorable herbicidal potency for compound 23 with a broad spectrum and acceptable crop selectivity against cotton at the dosage of 30-120 g ai/ha. Thus, compound 23 possessed a promising prospect as a novel HPPD-inhibiting herbicide candidate for cotton fields.
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 71
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 36977356
- Full Text :
- https://doi.org/10.1021/acs.jafc.2c08448