Synthesis and antifungal evaluation of 6-(N-arylamino)-7-methylthio-5,8-quinolinediones.

A series of 6-(N-arylamino)-7-methylthio-5,8-quinolinedione derivatives 4a-4l was newly synthesized for the evaluation of antifungal activity. 6-(N-Arylamino)-7-methylthio-5,8-quinolinediones were prepared by regioselective nucleophilic substitution of 6,7-dichloro-5,8-quinolinediones with arylamines in the presence of Ce3+, and Na2S/dimethylsulfate. The MIC values of 4a-4l were determined for antifungal susceptibility in vitro against Candida species by agar streak method. The derivatives 4a-4l had generally potent antifungal activities against all human pathogenic fungi. Especially they had the most potent activity against C. krusei at 12.5-0.8 micrograms/ml. Compounds 4d, 4g, 4h, 4j and 4k had more potent antifungal activities than fluconazole. Compounds 4g and 4h completely inhibited the fungal growth at 0.8-6.3 micrograms/ml against all Candida species, while fluconazole inhibited the growth at 25 micrograms/ml. The compounds such as 4g and 4h containing an N-(4-bromo-2-methylphenyl)- or N-(4-bromo-3-methylphenyl)amino substituent exhibited the most potent antifungal activities.