Design and discovery of novel antifungal candidates with 1,3-Dicarbonyl as a promising pharmacophore

Abstract

BACKGROUND

Pongamol is a flavonoid natural product containing a 1,3-dicarbonyl structure, which has various biological activities and plays an important role as the main skeleton in new drug development. 1,3-dicarbonyl compounds are not only widely used as synthetic building blocks in many organic reactions, but also commonly found in natural products and active molecules in pharmaceuticals. Sixty-one dicarbonyl derivatives were designed and synthesized using the 1,3-dicarbonyl active fragment as a structural unit and their antifungal activities against six agricultural plant pathogens were determined. The compound ET-17 with the most significant activity against Botrytis cinerea was finally selected to study its preliminary mechanism of action.

RESULTS

Most fluorinated compounds exhibited significant antimicrobial activities against fungi. Among them, compounds ET-6, ET-17, EFM-6, EFM-7, EFM-8, BZ-11 and BZ-12 exhibited remarkable antifungal activity in vitro against plant pathogenic fungi. Especially, compound ET-17 displayed the broad-spectrum antifungal activities against Botrytis cinerea, Fusarium graminearum, Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium oxysporum and Phytophthora capsici with EC₅₀ values of 0.740, 0.635, 0.640, 1.732, 4.515 and 1.984 μg/mL, respectively. Further mechanism research results indicated that compound ET-17 might cause mycelial abnormality, cell membrane breakage, accumulation of reactive oxygen species (ROS) of B. cinerea to inhibit mycelial growth. Furthermore, the in vivo protection experiments showed that compound ET-17 had a certain protective effect (72.23%) at 100 μg/mL.

CONCLUSION

The 1,3-dicarbonyl derivatives showed efficient and broad-spectrum antifungal activities against six plant pathogens, which is expected to become a new broad-spectrum bactericidal candidate for controlling plant diseases. © 2025 Society of Chemical Industry.