Design, Synthesis and Antifungal Activities of Novel Quinazolinone Derivatives

Abstract

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 1 H NMR, 13 C NMR and HRMS. Preliminary in vitro antifungal test showed that the target compounds exhibited moderate to favourable 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.

Design, synthesis, and mechanism study of novel 1-arylisoquinoline derivatives as antifungal agents

“…Compound 4a-4h was condensed with Boc-glycine to obtain intermediate 5a-5h. Under acidic conditions, the Boc protective group was removed to obtain intermediate 6a-6h, and then condensed with heterocyclic acid 7a-7d amide to obtain target compounds A1-32 [23].…”