Fabrication of Versatile Pyrazole Hydrazide Derivatives Bearing a 1,3,4-Oxadiazole Core as Multipurpose Agricultural Chemicals against Plant Fungal, Oomycete, and Bacterial Diseases

Abstract

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds <b>a1</b>-<b>a6</b>, <b>b1</b>-<b>b3</b>, <b>b7</b>, <b>b10</b>, <b>b13</b>, and <b>b18</b>. For the antifungal activity, the minimal EC₅₀ values could afford 0.47 (<b>a2</b>), 1.05 (<b>a2</b>), 0.65 (<b>a1</b>), and 1.32 μg/mL (<b>b3</b>) against the corresponding fungi <i>Gibberella zeae</i> (<i>G. z.</i>), <i>Fusarium oxysporum</i>, <i>Botryosphaeria dothidea</i>, and <i>Rhizoctonia solani</i>. In vivo pot experiments against corn scab (caused by <i>G. z.</i>) revealed that the compound <b>a2</b> was effective with protective and curative activities of 90.2 and 86.3% at 200 μg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC₅₀ = 3.21 μM, <b>a2</b>) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds <b>b2</b> and <b>a4</b> yielded superior anti-oomycete and antibacterial activities toward <i>Phytophora infestins</i> and <i>Xanthomonas oryzae pv. oryzae</i> with EC₅₀ values of 2.92 and 8.43 μg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (<b>a4</b>) at 200 μg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.