Design, Synthesis, Antifungal Activity, and Action Mechanism of Indole-Oxazole Compounds as Potential Fungicides.

Abstract

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.