DISCOVERY OF TRIKETONE-QUINOXALINE HYBRIDS AS POTENT HPPD INHIBITORS USING STRUCTURE-BASED DRUG DESIGN

• HPPD is one of the most promising targets for new herbicides. A family novel inhibitors based on triketone-quinoxaline scaffold was designed and synthesized. One particular product (7d) gave highest inhibition newly synthesized derivatives. Triketone-quinoxaline derivatives provide a useful molecular discovery HPPD-inhibiting p-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) belongs to Fe(II)-dependent non-heme oxygenases that occur in majority aerobic organisms. has proved be target herbicide research development. battery compounds been using structure-based drug design strategy then prepared. Enzyme assays show these possess favorable capability against Arabidopsis thaliana with IC50 values ranging from 0.317 0.891 μmol·L−1. Subsequently, docking results indicate two adjacent carbonyls triketone moiety representative compound 2-(2,3-dimethyl-8-(o-tolyl)quinoxaline-6-carbonyl)-3-hydroxycyclohex-2-en-1-one engage chelation ferrous ion A. bidentate pose, its quinoxaline forms sets parallel π-stacking interaction between phenylalanine residues (Phe424 Phe381). In addition, extended phenyl group also interacts Phe392 π-π stacking way. This study indicates discovering substantially increased potency, providing insight into