Design, Synthesis, and Bioactivity of Novel Coumarin-3-carboxylic Acid Derivatives Containing a Thioether Quinoline Moiety

A series of coumarin-3-carboxylic acid derivatives containing a thioether quinoline moiety were designed and synthesized. The structures of these compounds were determined using ¹H NMR, ¹³C NMR, and HRMS. The antibacterial activity of the compounds was evaluated against <i>Xanthomonas oryzae</i> pv <i>oryzae</i> (<i>Xoo</i>), <i>Ralstonia solanacearum</i> (<i>Rs</i>), and <i>Acidovorax citrulli</i> (<i>Aac</i>). The results showed that most of the compounds exhibited significant antibacterial activity against these pathogens. Particularly, compound A9 demonstrated potent activity against <i>Xoo</i> and <i>Aac</i>, with EC₅₀ values of 11.05 and 8.05 μg/mL respectively. In addition, A9 indicated strong protective and curative effects against <i>Aac in vivo</i>, with efficacy rates of 61.50 and 54.86%, respectively, surpassing those of the positive control thiodiazole copper. The scanning electron microscopy observations revealed that treatment of <i>Aac</i> cells with A9 at a concentration of 2EC₅₀ resulted in a curved and sunken cell morphology, along with destroyed cell membrane integrity. Additionally, the motility and exopolysaccharide production of <i>Aac</i> were inhibited, and biofilm formation was prevented. Consequently, these newly developed derivatives of coumarin-3-carboxylic acid, incorporating the thioether quinoline moiety, hold promise as potential templates for the development of innovative antibacterial agents.