Fungicidal/Bactericidal Activities Study Of N-Aryl-Pyridine-4-Ones

Fungicides are widely used in agriculture,which make a great contribution to agricultural production.However,in recent years,the problem with fungicide resistance is becoming more and more serious.Moreover there are many kinds and complex properties of fungicides,which are inconvenient in practical production and application.Therefore,the ideal fungicide must not only be highly effective,broad-spectrum and low-risk,but also difficult to produce resistance,it is best to have both antibacterial and antifungal activities.For this reason,taking inspiration from natural products is an effective way to create novel fungicides that meet current needs.So 33 N-aryl-pyridine-4-ones derivatives were designed and synthesized by using maltol and antidesmone as lead compounds,and their fungicidal/bactericidal activities were tested in order to obtain ideal fungicides.Measurements of the antifungal activity of N-aryl-pyridine-4-ones have shown that most of these compounds show significant antifungal activity in vitro.Especially,compound23 has more than 90%inhibitory activity against 9 plant pathogenic fungi at 50?g mL^-1,which is superior to azoxystrobin.The analysis of structure-activity relationship shows that the hydroxyl and methyl groups on the pyridone ring are essential for the fungicidal activity of compounds;different aryl groups have a great influence on the activity of compounds,among which the para-alkyl substitution on the benzene ring has an optimal effect,and the greater the steric hindrance or the longer the carbon chain,the stronger the activity of compounds;the meta-disubstituted on the benzene ring significantly enhances the activity of compounds,and the combination of meta-dihalogen substitution and para-alkyl substitution can further increase the activity of compounds.Moreover,the in vivo bioassay also demonstrated that compound 23 achieved an over95%control effect against Corynespora cassiicola,Pseudoperonospora cubensis,Fusarium graminearum and Botrytis cinerea at 400?g mL^-1.At the same time,compound 23 had excellent protective activities against Botryodiplodia theobromae?protective effect was88.89%?and Colletotrichum musae?protective effect was 93.57%?at 200?g mL^-1.Mango post-harvest preservation experiment results show that compound 23 can effectively control postharvest diseases of mango?control effect was 87.91%,day 14?at 200?g mL^-1 and extend the preservation time of mangoes.In addition,it was found that compounds 22 and 23 can also effectively control rice bacterial leaf blight.The in vitro antibacterial activity of compounds 22 and 23 was 84.54%and 83.93%?100?g mL-1?,which was similar to Zhongshengmycin?86.09%?.At 200?g mL^-1,the in vivo curative activity?49.30%and 52.42%,respectively?and protective activity?50.37%and 52.70%,respectively?of compounds 22,23 were even higher than Zhongshengmycin?curative activity was 42.90%and protective activity was 40.80%?.Considering the safety of the compound 23,we also evaluated its cytotoxicity against LO-2 cell line,a normal human hepatic cell line.The results proved that compound 23demonstrated very weak cytotoxicity against LO-2 cell line with the inhibition rate of 29.68%at highest concentration of 2000?g mL^-1.N-aryl-pyridine-4-ones have been reported for the first time to be able to control plant pathogenic fungi/bacteria,and their new skeleton structure has a broad development prospect.Compound 23 has high-efficiency and broad-spectrum antifungal activity and excellent antibacterial activity.Its novel structure may also have new mechanism of action.Therefore,compound 23 meets the requirements of ideal fungicides,and can be used to develop potential agrochemical fungicides and bactericides.