Design, Synthesis, Antibacterial Activity, and Mechanism of Novel Mesoionic Compounds Based on Natural Pyrazole Isolated from an Endophytic Fungus <i>Colletotrichum gloeosporioides</i>

Abstract

<i>Xanthomonas oryzae</i> pv. <i>oryzicola</i> (<i>Xoo</i>) is a type of bacteria that causes bacterial leaf blight disease in rice plants. This disease is substantially harmful, and the current prevention and control measures are facing challenges. This study has investigated the effectiveness of the control activity that the endophytic fungus NS7 fermented from <i>Dendrobium candidum</i> possessed against <i>Xoo</i>. Twenty-eight novel mesoionic compounds were designed and synthesized based on the natural compound <b>D</b>. These compounds displayed moderate to excellent anti-<i>Xoo</i> activity <i>in vitro</i>. Notably, compound <b>24</b> exhibited prominent anti-<i>Xoo</i> activity <i>in vitro</i> with an EC₅₀ value of 40.3 mg/L, which was better than that of the positive control thiodiazole copper (TC)(71.2 mg/L) and the lead compound <b>D</b> (108.1 mg/L). <i>In vivo</i> pot experiments on <i>Xoo</i> showed that compound <b>24</b> exhibited protective and curative activities of 39.4 and 30.4%, respectively, which were better than those of TC (35.7 and 28.8%, respectively). Further, a preliminary mechanism study indicated that compound <b>24</b> could enhance the activity of defense enzymes to improve the ability for anti-<i>Xoo</i>. Meanwhile, compound <b>24</b> could also regulate the carbon fixation in photosynthetic organisms, which might be related to the enhanced immune function of rice. This study offers a new strategy for discovering antibacterial agents based on natural products.