Discovery of novel D/L-camphor derivatives containing oxime ester as fungicide candidates: Antifungal activity, structure-activity relationship and preliminary mechanistic study
Peng Dai, Zihua Ma, Huizhen Xue, Kaili Xie, Yufei Li, Yafang Sun, Qing Xia, Ming‐Zhi Zhang, Yu‐Cheng Gu, Weihua Zhang
Abstract
To develop new environmentally friendly fungicides, we designed and synthesized a novel series of D/L-configured camphor oxime ester derivatives based on the natural product camphor as a lead compound. We investigated the in vitro antifungal activity of these compounds against six common plant pathogenic fungi. Among them, compounds B1-6, B1-17 and B2-6 displayed great in vitro activity against Rhizoctonia solani with EC 50 values of 7.28, 4.64, and 7.62 μg/mL. The HOMO and LUMO calculations indicated that strong electron-withdrawing halogen elements exhibit better activity compared to electron-donating alkyl groups. Preliminary mechanistic studies, using SEM and TEM, indicated that compound B1-17 induced disordered entanglement of hyphae, shrinkage of hyphal surfaces, and vacuole swelling and rupture, which disrupted normal hyphal growth. Additionally, compound B1-17 induced the production and accumulation of ROS, disrupted MMP, and effectively inhibited the germination and formation of sclerotia in Rhizoctonia solani . These compounds hold potential as new antifungal agents for further research. • A series of novel camphor derivatives were designed and synthesized. • Some compounds showed excellent antifungal activity in primary assays. • R. solani cells treated with B1-17 showed abnormal ultrastructure. • HOMO and LUMO used to explore structure-activity relationships of these derivatives. • Highly active compounds analyzed by ROS, MMP, SEM, and TEM.