Pinonic Acid Derivatives Containing Thiourea Motif: Promising Antifungal Lead Compound Targeting Cellular Barrier of .

In order to explore novel antifungal lead compounds from plant essential oil, thirty-two pinonic acid derivatives containing thiourea groups were designed and synthesized using α-pinene as a raw material. One of these pinonic acid derivatives compound exhibited noteworthy antifungal activity against (EC = 9.22 mg/L), which was comparable to that of the positive control kresoxim-methyl (EC = 9.69 mg/L). Structure-activity relationship (SAR) studies demonstrated that the introduction of thiourea groups, F atoms, and Cl atoms into the structure of pinonic acid derivatives significantly improved their antifungal activity. The antifungal test revealed that compound could effectively control pear anthracnose. It also proved that compound showed low acute oral toxicity to honeybees (LD > 100 μg/bee) and low or no cytotoxicity to LO2 and HEK293 cell lines. The preliminary mechanism of action studies revealed that compound caused mycelium deformity, increased cell membrane permeability, blocked the normal process of phospholipase C on the cell membrane, and reduced mycelium protein content. The results of molecular docking studies demonstrated the stable binding of compound to phospholipase C and chitin synthetase. This study suggested that compound could be used as a promising lead compound for the development of novel antifungal agents targeting the cellular barrier of .