Fragments recombination, design, synthesis, safener activity and CoMFA model of novel substituted dichloroacetylphenyl sulfonamide derivatives.

Abstract

Isoxaflutole (IXF), as a kind of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many kinds of plants. IXF can cause injury in corn including leaf and stem bleaching, plant height reduction or stunting, and reduced crop stand. Safeners are co-applied with herbicides to protect crops without compromising weed control efficacy. With the ultimate goal of addressing Zea mays injury caused by IXF, a series of novel substituted dichloroacetylphenyl sulfonamide derivatives was designed on the basis of scaffold hopping and active substructure splicing. A total of 35 compounds were synthesized via acylation reactions. All the compounds were characterized by infrared (IR), proton and carbon-13 nuclear magnetic resonance (1 H-NMR and 13 C-NMR), and high-resolution mass spectrometry (HRMS). The configuration of compound II-1 was confirmed by single crystal X-ray diffraction. The bioassay results showed that all the title compounds displayed remarkable protection against IXF via improved content of carotenoid. Especially compound II-1 which possessed better glutathione transferases (GSTs) activity and carotenoid content than the contrast safener cyprosulfamide (CSA). All the satisfied parameters suggested that the Comparative Molecular Field Analysis (CoMFA) model was reliable and stable [with a cross-validated coefficient (q2 ) = 0.527, r2 = 0.995, r2 pred = 0.931]. The molecular docking simulation indicated that the compound II-1 and CSA could compete with diketonitrile (DKN) at the active site of HPPD, which is a hydrolyzed product of IXF in plants, causing the herbicide to be ineffective. The present work revealed that the compound II-1 deserves further attention as the candidate structure of safeners. © 2020 Society of Chemical Industry.