Design, Synthesis, Antifungal Activity, and Action Mechanism of Indole–Oxazole Compounds as Potential Fungicides
Wei Zhan, Zhiyang Mei, Mingxia Dan, Zhuojia Zhang, Jinliang Zhou, Yue Liu, Huiwen Zhou, Yujie Zhou, Dingding Lü, Rui Zhu, Shaojun ZhengAbstract
Starting from 1H-indole-3-carbaldehyde, 19 indole oxazole alkaloid analogues were synthesized in excellent yields. The results of bioassays showed that compound Z-2 possessed potent activity against Rhizoctonia solani and Botrytis cinereaPers with EC50 values of 7.03 and 13.5 mg/L, respectively. Compound Z-3 (EC50 = 6.81 mg/L) exhibited significant activity against Sclerotinia sclerotiorum. In vivo antifungal bioassays suggested that compounds Z-2 and Z-3 could serve as novel agricultural antifungals. Cell membrane permeability and PI staining experiments demonstrated that compounds Z-2 and Z-3 impaired hyphal membrane integrity, leading to cytoplasmic leakage and suppression of hyphal growth. SEM and TEM revealed that compound Z-2 induced distinct morphological alterations in the hyphae, thereby suppressing hyphal growth. Molecular docking and DFT calculations confirmed that compounds Z-2 and Z-3 share highly similar binding modes. Plant safety tests verified their low phytotoxicity. The easy accessibility and cost-effectiveness demonstrated the practical potential of indole-oxazole derivatives as a new model for agrochemical innovation.