Plant pathogenic fungi have caused enormous yield and economic losses in agricultural production. In order to discover effective antifungal agents, a series of 19 novel quinazolinone derivatives 7 were designed and synthesized based on molecular splicing approach. The classical pharmacophore of amide was introduced into N-1 of quinazolinone skeleton. The structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. Preliminary in vitro antifungal test showed that the target compounds exhibited moderate to favorable activities against six kind of plant pathogenic fungi at the concentration of 50 mg/L. Compound 7a had significant inhibitory effects on Fusarium graminearum and Rhizoctonia solani with EC₅₀ of 12.727 and 12.413 mg/L, respectively, which were better than chlorothalonil (14.323 and 13.339 mg/L). Molecular electrostatic potential of 7a indicated that the amide moieties located in the negative potential region and might generate hydrogen bond with target amino acid residue. The above results provided an effective strategy for the development of quinazolinone antifungal agents.

Key words: quinazolinone, quinazolinone alkaloids, amide, antifungal activity, molecular electrostatic potential