Synthesis and Biological Activity of Myricetin Derivatives Containing Pyrazole Piperazine Amide

Abstract

In this paper, a series of derivatives were synthesized by introducing the pharmacophore pyrazole ring and piperazine ring into the structure of the natural product myricetin through an amide bond. The structures were determined using carbon spectrum and hydrogen spectrum high-resolution mass spectrometry. Biological activities of those compounds against bacteria, including Xac (Xanthomonas axonopodis pv. Citri), Psa (Pseudomonas syringae pv. Actinidiae) and Xoo (Xanthomonas oryzae pv. Oryzae) were tested. Notably, D6 exhibited significant bioactivity against Xoo with an EC50 value of 18.8 μg/mL, which was higher than the control drugs thiadiazole-copper (EC50 = 52.9 μg/mL) and bismerthiazol (EC50 = 69.1 μg/mL). Furthermore, the target compounds were assessed for their antifungal activity against ten plant pathogenic fungi. Among them, D1 displayed excellent inhibitory activity against Phomopsis sp. with an EC50 value of 16.9 μg/mL, outperforming the control agents azoxystrobin (EC50 = 50.7 μg/mL) and fluopyram (EC50 = 71.8 μg/mL). In vitro tests demonstrated that D1 possessed curative (60.6%) and protective (74.9%) effects on postharvest kiwifruit. To investigate the active mechanism of D1, its impact on SDH activity was evaluated based on its structural features and further confirmed through molecular docking. Subsequently, the malondialdehyde content of D1-treated fungi was measured, revealing that D1 could increase malondialdehyde levels, thereby causing damage to the cell membrane. Additionally, the EC50 value of D16 on P. capsici was 11.3 μg/mL, which was superior to the control drug azoxystrobin (EC50 = 35.1 μg/mL), and the scanning electron microscopy results indicated that the surface of drug-treated mycelium was ruffled, and growth was significantly affected.