Design, Synthesis, Structure–Activity Relationship, Molecular Docking, and Herbicidal Evaluation of 2-Cinnamoyl-3-Hydroxycyclohex-2-en-1-one Derivatives as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Abstract

Cinnamic acid, isolated from cinnamon bark, is a natural product with excellent bioactivity, and it effectively binds with cyclohexanedione to form novel 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors. According to the active sub-structure combination principle, a series of novel 3-hydroxy-2-cinnamoyl-2-en-1-one derivatives were designed and synthesized. The title compounds were characterized by infrared, 1H NMR, 13C NMR, and HRMS. The in vitro inhibitory activity of AtHPPD verified that compound II-13 showed the most activity with a half-maximal inhibitory concentration (IC50) value of 0.180 μM, which was superior to that of mesotrione (0.206 μM) in vitro. The preliminary herbicidal activity tests demonstrated that some compounds had good herbicidal activity especially compound II-13 at a concentration of 150 g ai/ha. The binding mode of AtHPPD through molecular docking indicated that two oxygens of compounds II-13 formed bidentate interactions with metal ions, and the benzene ring formed π-π accumulation effects with Phe-381 and Phe-424. The results of molecular dynamics simulations showed that compound II-13 exhibited a more stable binding ability with AtHPPD than mesotrione. This study provided insights into the development of natural and efficient herbicides in the future.

Design, Synthesis, and Herbicidal Activity of Diphenyl Ether Derivatives Containing a Five-Membered Heterocycle

“…The PPO catalytic rate was computed by determining the modification in the concentration of proto IX within a certain duration of time. The enzymatic inhibition rate of enzymes by different target compounds was calculated by the following formula 47,48…”

“…The PPO catalytic rate was computed by determining the modification in the concentration of proto IX within a certain duration of time. The enzymatic inhibition rate of enzymes by different target compounds was calculated by the following formula , where I is the PPO restraint efficiency, a is the catalytic rate of the enzyme without the target compound, and b is the catalytic rate of the enzyme after adding the target compound. The restraint efficiency at various concentrations was determined by fixing the substrate concentration and altering the tested compound concentration.…”

Fabrication and Characterization of Antifungal Hydroxypropyl-β-Cyclodextrin/Pyrimethanil Inclusion Compound Nanofibers Based on Electrospinning

“…It was reasonably optimized before computing the Gasteiger–Huckel charge for aforesaid molecules. In Discovery Studio Client, the “CDOCKER” method was adopted for docking modeling. , A CHARMM force field was applied to the structure to remove water prior to docking. The binding site in the molecular structure of HPβCD was identified during the docking process, and its subregion was 13.0 Å from the center of the ligand.…”

Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

“…Computer technology promotes drug development and provides theoretical guidance for drug design. Topomer comparative molecular field analysis (Topomer CoMFA), a combination of the initial “Topomer” method and CoMFA technology with 3D-quantitative structure-activity relationship (3D-QSAR) technology and autocomplete regression analysis can be used to predict the physicochemical properties or biological activity of compounds and screen the database [ 14 , 15 ]. Topomer CoMFA model has been widely used in drug design, such as for Alzheimer’s disease, human immunodeficiency virus (HIV), hypercholesterolemia, and breast, lung or renal cell carcinoma [ 16 , 17 , 18 , 19 ].…”