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 (1)H 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 EC(50) values ranging from 8.3 to 64.2 microg/mL. After treating F. oxysporum with compound 3g at 100 microg/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 microg/mL within 12h, the mycelial reducing sugar, D-GlcNAc, content and chitinase activity decline, but the soluble protein content shows no obvious change.
Xu
Guang-Fang
GF
Center for Research and Development of Fine Chemicals, Key Laboratory of Green Pesticide and Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
Song
Bao-An
BA
Bhadury
Pinaki S
PS
Yang
Song
S
Zhang
Pei-Quan
PQ
Jin
Lin-Hong
LH
Xue
Wei
W
Hu
De-Yu
DY
Lu
Ping
P
D000117:Acetylglucosamine / Q000378:metabolism; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002688:Chitinases / Q000032:analysis / Q000378:metabolism; D048271:Chitosan / Q000032:analysis / Q000378:metabolism; D005658:Fungi / Q000187:drug effects*; D005670:Fusarium / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D025282:Mycelium / Q000187:drug effects / Q000254:growth & development; D010539:Permeability / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000935:Antifungal Agents; D011799:Quinazolines; D013438:Sulfhydryl Compounds; D048271:Chitosan; D002688:Chitinases; D000117:Acetylglucosamine