Design, Synthesis, Herbicidal Activity, and Molecular Docking Study of 2-Thioether-5-(Thienyl/Pyridyl)-1,3,4-Oxadiazoles as Potent Transketolase Inhibitors

Abstract

Transketolase (TK) has been regarded as a new target for the development of novel herbicides. In this study, a series of 2-thioether-5-(thienyl/pyridyl)-1,3,4-oxadiazoles were designed and synthesized based on TK as the new target. The preliminary bioassay results indicated that compounds <b>4l</b> and <b>4m</b> displayed the best herbicidal activities against <i>Amaranthus retroflexus</i> (<i>AR</i>) and <i>Digitaria sanguinalis</i> (<i>DS</i>), with the inhibition exceeding 90% at 100-200 mg/L <i>in vitro</i>. Moreover, they also displayed higher postemergence herbicidal activities (90% control) against <i>AR</i> and <i>DS</i> than all of the positive controls at 45-90 g [active ingredient (ai)]/ha in a greenhouse. Notably, compounds <b>4l</b> and <b>4m</b> showed a broad spectrum of weed control at 90 g ai/ha. More significantly, compound <b>4l</b> exhibited good crop selectivity against maize at 90 g ai/ha. Both fluorescent binding experiments and molecular docking analyses indicated that compounds <b>4l</b> and <b>4m</b> exhibited strong TK inhibitory activities with superior binding affinities than the others. Preliminary mechanism studies suggested that they might exert their TK inhibitory effects by occupying the active cavity of <i>At</i> TK and forming more strong interactions with amino acids in the active site. Taken together, these results suggested that compound <b>4l</b> was a potential herbicide candidate for weed control in maize fields targeting TK.