Unlocking nature's potential: Novel isomagnolone analogues as broad-spectrum antimicrobial agents for plant disease control

Abstract

In an effort to develop novel, less toxic, and effective controls for plant diseases, we aimed to identify derivatives of the natural product isomagnolone with antimicrobial activity. We established a facile method for the synthesis of isomagnolone and its isomer Ⅱ, and prepared a series of novel isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides Ⅲ1–30. The structures of Ⅲ1–30 were determined by IR, 1H NMR, 13C NMR, and ESI-MS. Among them, compounds Ⅲ24 and Ⅲ26 exhibited potent antifungal activity against four fungi with EC50 values substantially lower than that of the positive control, hymexazol. Additionally, the antibacterial results showed that Ⅲ20 and Ⅲ22 displayed more potent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) with EC50 values of 12.6 and 10.3 ​μg/mL, respectively, approximately 2-fold lower than that of the positive control, thiodiazole copper (EC50: 24.0 ​μg/mL). Structure-activity relationships suggested that the antifungal activity of title isomagnolone analogues was favored when the substituent (R) was pyridyl or the 2-chloro-3-pyridyl group. Mechanism of action studies revealed that Ⅲ22 could disrupt bacterial membranes, thus resulting in cell death. Furthermore, the potent compounds Ⅲ20, Ⅲ22, Ⅲ24, and Ⅲ26 showed low toxicity against the human hepatocyte cell line (LO2). Given these results, these isomagnolone analogues bearing N-(1,3-thiazol-2-yl)amides are promising antimicrobials against phytopathogenic fungi and bacteria for controlling plant diseases.