Design, Synthesis,\nand Bioactivity of Novel Coumarin-3-carboxylic\nAcid Derivatives Containing a Thioether Quinoline Moiety

A series of coumarin-3-carboxylic\nacid derivatives containing\na\nthioether quinoline moiety were designed and synthesized. The structures\nof these compounds were determined using <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS. The antibacterial activity of the compounds was\nevaluated against Xanthomonas oryzae pv <i>oryzae</i> (<i>Xoo</i>), Ralstonia solanacearum (<i>Rs</i>), and Acidovorax citrulli (<i>Aac</i>). The results\nshowed that most of the compounds exhibited significant antibacterial\nactivity against these pathogens. Particularly, compound A9 demonstrated\npotent activity against <i>Xoo</i> and <i>Aac</i>, with EC<sub>50</sub> values of 11.05 and 8.05 μg/mL respectively.\nIn addition, A9 indicated strong protective and curative effects against <i>Aac in vivo</i>, with efficacy rates of 61.50 and 54.86%, respectively,\nsurpassing those of the positive control thiodiazole copper. The scanning\nelectron microscopy observations revealed that treatment of <i>Aac</i> cells with A9 at a concentration of 2EC<sub>50</sub> resulted in a curved and sunken cell morphology, along with destroyed\ncell membrane integrity. Additionally, the motility and exopolysaccharide\nproduction of <i>Aac</i> were inhibited, and biofilm formation\nwas prevented. Consequently, these newly developed derivatives of\ncoumarin-3-carboxylic acid, incorporating the thioether quinoline\nmoiety, hold promise as potential templates for the development of\ninnovative antibacterial agents.