Biological Activity And Structure-activity Relationship Of Frutione A And The Analogous Compounds

Frutinone A also known as chromene[4,3-b]chromene-6,7-dione,is a flavonoid compound that is widely found in plants of the Frutinone Amily Polygalaceae,and it is a drug molecule and lead compound.In this study,ten derivatives were designed and synthesized using the natural product Frutinone A as a template.The obtained compounds were structurally characterized by ¹H-NMR,¹³CNMR and HR-MS.The inhibition activities of the synthesized compounds against 28 plant pathogenic fungi in vitro were determined by mycelial growth rate method,and the inhibition activities and conformational relationships of the Frutinone A compounds were analyzed and discussed to investigate the potent effect of Frutinone A and its derivatives against rice blast.The main studies were as follows:1.Frutinone A has excellent inhibition activity against Verticillium dahliae Kleb,Fusariumnseucouramineuru,Colletotrichum graminicola Wilson,Colletotrichum gloeosnorioides,Rhizoctonia solani Kühn,Rhizoctonia solani,Selerotium rolfsii,Fusarium monilitoume Sheld,Fuasarum graminearum and Pyriculariaoryae Cay,etc.Its activity against Fusariumnseucouramineuru(EC₅₀=0.046mmol/L),Rhizoctonia solani(EC₅₀=0.057 mmol/L)and Fusarium monilitoume Sheld(EC₅₀=0.031 mmol/L)was higher than that of the biopesticide phenazine-1-carboxylic acid,and significantly higher than that of coumarins compounds:4-hydroxycoumarin.2.Among the derivatives synthesized with Frutinone A as the lead compound,compound 11-methyl-6H,7H-chromeno[4,3-b]chromene-6,7-dione（f-1）was 1-5 times more active than Frutinone A against Selerotium rolfsii,Rhizoctonia solani kühn,Colletotrichum graminicola（Cesati）Wilson,and Fuasarum graminearum.The in vitro inhibitory activity of these derivatives against Colletotrichum graminicola Wilson(EC₅₀=0.017mmol/L),Fusarium monilitoume Sheld(EC₅₀=0.025mmol/L),Verticillium dahliae Kleb(EC₅₀=0.079mmol/L),Rhizoctonia solani Kühn(EC₅₀=0.015 mmol/L),Fuasarum graminearum(EC₅₀=0.016 mmol/L)were significantly higher than that of the biopesticide phenazine-1-carboxylic acid.The preliminary structure activity relationship discussion showed that the A ring was the active center and the substituent electron donating group on the A ring was more active than the substituent electron withdrawing group.The activity was generally reduced after the substitution of the B ring and the B ring substituent electron withdrawing group was more effective than the substituent electron donating group,and the in vitro inhibitory activity of the A ring transformation was significantly higher than that of the B ring transformation.3.The results of pot experiments showed that:Frutinone A and its derivative f-1 had better control effect on rice sheath blight.At the treatment concentration of 0.2 mmol/L,the efficacy of Frutinone A（39.81%）against rice sheath blight was slightly lower than that of phenazine-1-carboxylic acid（43.77%）,and the efficacy of compound f-1（53.40%）against rice sheath blight was higher than that of phenazine-1-carboxylic acid.At a treatment concentration of 0.5 mmol/L,compound f-1（73.13%）was more effective than phenazine-1-carboxylic acid（69.77%）against rice sheath blight.In conclusion,Frutinone A and some of its derivatives have good in vitro inhibitory activity against a variety of plant pathogenic fungi and can effectively control rice sheath blight.The structural modification and bioactivity studies with Frutinone A as the parent can provide theoretical basis for the development and utilization of such plant-derived fungicides.