Dai Peng, Ma Zihua, Yi Guangfu, Li Yufei, Xie Kaili, Sun Yafang, Xia Qing, Liu Zewen, Zhang Weihua
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing, China.
College of Economics and Management, Huaibei Institute of Technology, Huaibei, China.
Pest Manag Sci. 2025 Feb;81(2):786-797. doi: 10.1002/ps.8481. Epub 2024 Oct 18.
Succinate dehydrogenase inhibitors (SDHIs) have rapidly become one of the fastest-growing categories of fungicides used against plant pathogenic fungi. Recent research advancements have emphasized that structural modifications of SDHIs using naturally sourced scaffolds represent an innovative strategy for developing new, highly effective, broad-spectrum fungicides. A novel series of d/l-camphorhydrazide derivatives potentially targeting fungal succinate dehydrogenase (SDH) were designed, synthesized and evaluated for their antifungal effects against Rhizoctonia solani, Fusarium graminearum, Valsa mali and Botrytis cinerea.
Amongst them, compounds A1-7 (d-camphor) and A2-7 (l-camphor) displayed excellent in vitro activity against R. solani with median effective concentration (EC) values of 0.38 and 0.48 μg mL, which were obviously superior to that of boscalid (0.87 μg mL). A2-5 (l-camphor, EC = 3.27 μg mL) exhibited good activity against V. mali. A2-7 (2.13 μg mL1), A2-21 (5.2 μg mL) and A1-5 (5.15 μg mL) showed good antifungal activity against F. graminearum with EC values below that of boscalid (5.85 μg mL). Preliminary mechanistic studies, using scanning and transmission electron microscopy, indicated that compound A1-7 induced disordered entanglement of hyphae, shrinkage of hyphal surfaces, and vacuole swelling and rupture, which disrupted normal hyphal growth. Additionally, compound A1-7 induced the production and accumulation of reactive oxygen species, disrupted mitochondrial membrane potential, and effectively inhibited the germination and formation of sclerotia in R. solani. Moreover, the molecular docking results and SDH enzyme assays yielded promising outcomes.
In this study, the designed and optimized compounds A1-7 and A2-7 emerged as promising candidates for SDH-targeting fungicides, demonstrating strong antifungal activity. These compounds hold potential as new antifungal agents for further research. © 2024 Society of Chemical Industry.
琥珀酸脱氢酶抑制剂（SDHIs）已迅速成为用于防治植物病原真菌的增长最快的杀菌剂类别之一。最近的研究进展强调，利用天然来源的骨架对SDHIs进行结构修饰是开发新型、高效、广谱杀菌剂的一种创新策略。设计、合成了一系列可能靶向真菌琥珀酸脱氢酶（SDH）的新型d/l-樟脑酰肼衍生物，并评估了它们对立枯丝核菌、禾谷镰刀菌、苹果腐烂病菌和灰葡萄孢的抗真菌效果。
其中，化合物A1-7（d-樟脑）和A2-7（l-樟脑）对立枯丝核菌表现出优异的体外活性，半数有效浓度（EC）值分别为0.38和0.48μg/mL，明显优于啶酰菌胺（0.87μg/mL）。A2-5（l-樟脑，EC = 3.27μg/mL）对苹果腐烂病菌表现出良好活性。A2-7（2.13μg/mL）、A2-21（5.2μg/mL）和A1-5（5.15μg/mL）对禾谷镰刀菌表现出良好的抗真菌活性，EC值低于啶酰菌胺（5.85μg/mL）。使用扫描电子显微镜和透射电子显微镜进行的初步机理研究表明，化合物A1-7诱导菌丝无序缠结、菌丝表面收缩以及液泡肿胀和破裂，从而破坏正常的菌丝生长。此外，化合物A1-7诱导活性氧的产生和积累，破坏线粒体膜电位，并有效抑制立枯丝核菌菌核的萌发和形成。此外，分子对接结果和SDH酶分析产生了有前景的结果。
在本研究中，设计和优化的化合物A1-7和A2-7成为有前景的靶向SDH的杀菌剂候选物，表现出强大的抗真菌活性。这些化合物作为新型抗真菌剂具有进一步研究的潜力。© 2024化学工业协会
