A novel simple 1,3,4-oxadiazole-2-carbohydrazide was reported to discover low-cost and versatile antifungal agents. Bioassay results suggested that a majority of the designed compounds were extremely bioactive against four types of fungi and two kinds of oomycetes. This extreme bioactivity was highlighted by the applausive inhibitory effects of compounds 4b, 4h, 5c, 5g, 5h, 5i, 5m, 5p, 5t, and 5v against Gibberella zeae, affording EC 50 values ranging from 0.486 to 0.799 μg/mL, which were superior to that of fluopyram (2.96 μg/mL) and comparable to those of carbendazim (0.947 μg/mL) and prochloraz (0.570 μg/mL). Meanwhile, compounds 4g, 5f, 5i, and 5t showed significant actions against Fusarium oxysporum with EC 50 values of 0.652, 0.706, 0.813, and 0.925 μg/mL, respectively. Pharmacophore exploration suggested that the N′phenyl-1,3,4-oxadiazole-2-carbohydrazide pattern is necessary for the bioactivity. Molecular docking of 5h with succinate dehydrogenase (SDH) indicated that it can completely locate the inside of the binding pocket via hydrogen-bonding and hydrophobic interactions, revealing that this novel framework might target SDH. This result was further verified by the significant inhibitory effect on SDH activity. In addition, scanning electron microscopy patterns were performed to elucidate the anti-G. zeae mechanism. Given these features, this type of framework is a suitable template for future exploration of alternative SDH inhibitors against plant microbial infections.

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 a1–a6, b1–b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 μg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 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, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae 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% (a4) at 200 μg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.

Plant bacterial diseases can potentially damage agricultural products around the world, and few effective bactericides can manage these infections. Herein, to sequentially explore highly effective antibacterial alternatives, 1,2,3-triazole-tailored carbazoles were rationally fabricated. These compounds could suppress the growth of three main intractable pathogens including Xanthomonas oryzae pv oryzae (Xoo), X. axonopodis pv citri (Xac), and Pseudomonas syringae pv actinidiae (Psa) with lower EC50 values of 3.36 (3p), 2.87 (3p), and 4.57 μg/mL (3r), respectively. Pot experiments revealed that compound 3p could control the rice bacterial blight with protective and curative efficiencies of 53.23% and 50.78% at 200 μg/mL, respectively. Interestingly, the addition of 0.1% auxiliaries such as organic silicon and orange oil could significantly enhance the surface wettability of compound 3p toward rice leaves, resulting in improved control effectiveness of 65.50% and 61.38%, respectively. Meanwhile, compound 3r could clearly reduce the white pyogenic exudates triggered by Psa infection and afforded excellent control efficiencies of 79.42% (protective activity) and 78.74% (curative activity) at 200 μg/mL, which were quite better than those of commercial pesticide thiodiazole copper. Additionally, a plausible apoptosis mechanism for the antibacterial behavior of target compounds was proposed by flow cytometry, reactive oxygen species detection, and defensive enzyme (e.g., catalase and superoxide dismutase) activity assays. The current work can promote the development of 1,2,3-triazole-tailored carbazoles as prospective antibacterial alternatives bearing an intriguing mode of action.

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including −CH2–, −OCH2–, and −SCH2−) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC50) against Sclerotinia sclerotiorum, Botryosphaeria dothidea, Fusarium oxysporum, and Colletotrichun higginsianum could reach 1.29 (10a), 0.63 (8h), 1.50 (10i), and 2.09 (10i) μg/mL, respectively, which were slightly lower than those of carbendazim (EC50 were 0.69, 0.13, 0.55, and 0.80 μg/mL, respectively). Especially, compound 10h was extremely bioactive against Gibberella zeae (G. z.) with an EC50 value of 0.45 μg/mL. This outcome was better than that of fluopyram (3.76 μg/mL) and was similar to prochloraz (0.47 μg/mL). In vivo trials against the corn scab (infected by G. z.) showed that compound 10h had control activity of 86.8% at 200 μg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound 10h could inhibit the enzymatic activity of SDH in the G. z. strain with an IC50 value of 3.67 μM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward Phytophthora infestans afforded a minimal EC50 value of 3.22 μg/mL (10h); compound 4d could strongly suppress the growth of bacterial strains Xanthomonas axonopodis pv. citri and Xanthomonas oryzae pv. oryzae with EC50 values of 3.79 and 11.4 μg/mL, respectively; and compound 10a displayed some insecticidal activity toward Plutella xylostella. Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.

Xanthomonas spp. are important plant pathogens that seriously endanger crop yields and food security. RpfF is a key enzyme that is involved in the synthesis of diffusible signal factor (DSF) signals and predominates in the signaling pathway regulating quorum sensing (QS) in Xanthomonas. Currently, novel RpfF enzyme-based quorum sensing agents have been proposed as a promising strategy for the development of new pesticides. However, few reports are available that comprehensively summarize the progress in this field. Therefore, we provide a comprehensive review of the recent advances in DSF-mediated QS and recently reported inhibitors that are proposed as bactericide candidates to target the RpfF enzyme and control plant bacterial diseases.