Synthesis and Docking Study of <i>N</i>-(Cinnamoyl)-<i>N</i>′-(substituted)acryloyl Hydrazide Derivatives Containing Pyridinium Moieties as a Novel Class of Filamentous Temperature-Sensitive Protein Z Inhibitors against the Intractable <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> Infections in Rice

Abstract

<i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>) is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate <i>Xoo</i>-induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from <i>Xoo</i> may lead to the discovery of highly efficient and innovative anti-<i>Xoo</i> agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting <i>Xoo</i>FtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of <i>Xoo</i>. As such, a series of novel <i>N</i>-(cinnamoyl)-<i>N</i>'-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti-<i>Xoo</i> activity was determined. The bioassay results showed that compound <b>A₇</b> had excellent anti-<i>Xoo</i> activity (EC₅₀ = 0.99 mg L^-1) in vitro and distinct curative activity (63.2% at 200 mg L^-1) in vivo. Further studies revealed that these designed compounds were <i>Xoo</i>FtsZ inhibitors, validating by the reduced GTPase activity of recombinant <i>Xoo</i>FtsZ, the nonfilamentous <i>Xoo</i>FtsZ assembly observed in the TEM images, and the prolonged <i>Xoo</i> cells from the fluorescence patterns. Computational docking studies showed that compound <b>A₇</b> had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of <i>Xoo</i>FtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control <i>Xoo</i>-induced infections.