Synthesis and antifungal activity of novel s-substituted 6-fluoro-4-alkyl(aryl)thioquinazoline derivatives

6-Fluoro-4-quinazolinol is prepared by the cyclization reaction of 2-amino-5-fluorobenzoic acid and formamide. The resulting thiol obtained by treatment of hydroxyl group with phosphorus (V) sulfide is converted under phase transfer condition to 4-substituted 4-alkylthio-6-fluoroquinazoline derivatives by reaction with halide. The structures of the compounds are confirmed by elemental analysis, IR, and 1H NMR. Title compounds 3a, 3g, and 3h are found to possess good antifungal activities. Using the mycelial growth rate method in the laboratory, the mechanism of action of 3g against Fusarium oxysporum in vitro is studied. The results indicate that 3a, 3g, and 3h have high inhibitory effect on the growth of most of the fungi with EC50 values ranging from 8.3 to 64.2 μg/mL. After treating F. oxysporum with compound 3g at 100 μg/mL, only 6.5% of its spore bourgeoned. The permeability of the cell membrane increases along with the malformation of the hypha and condensation of its endosome. After treatment with compound 3g at 100 μg/mL within 12 h, the mycelial reducing sugar, d-GlcNAc, content and chitinase activity decline, but the soluble protein content shows no obvious change.

6-Fluoro-4-quinazolinol is prepared by the cyclization reaction of 2-amino-5-fluorobenzoic acid and formamide. The resulting thiol obtained by treatment of hydroxyl group with phosphorus (V) sulfide is converted under phase transfer condition to 4-substituted 4-alkylthio-6-fluoro quinazoline derivatives by reaction with halide. Title compounds 3a, 3g, and 3h are found to possess good antifungal activities. Using the mycelial growth rate method in the laboratory, the mechanism of action of 3g against Fusarium oxysporum in vitro is studied. The results indicate that 3a, 3g, and 3h have high inhibitory effect on the growth of most of the fungi with EC50 values ranging from 8.3 to 64.2 μg/mL.Figure optionsDownload as PowerPoint slide