SYNTHESIS AND ANTIFUNGAL EVALUATION OF 6-(N-ARYLAMINO)-7-METHYLTHIO-5,8-QUINOLINEDIONES

A series of 6-(N-arylamino)-7-methylthio-5,8-quinolined lone derivativ es 4a-4l was newly synthesized for the evaluation of antifungal activi ty. 6-(N-Arylamino)-7-methylthio-5,8-quinolinediones were prepared by regioselective nucleophilic substitution of 6,7-dichloro-5,8-quinoline diones with arylamines in the presence of Ce3+, and Na2S/dimethylsulfa te. The MIC values of 4a-4l were determined for antifungal susceptibil ity in vitro against Candida species by agar streak method. The deriva tives 4a-4l had generally potent antifungal activities against all hum an pathogenic fungi. Especially they had the most potent activity agai nst C, krusei at 12.5 similar to 0.8 mu g/ml. Compounds 4d, 4g, 4h, 4j and 4k had more potent antifungal activities than fluconazole. Compou nds 4g and 4h completely inhibited the fungal growth at 0.8 similar to 6.3 mu g/ml against all Candida species, while fluconazole inhibited the growth at 25 mu g/ml. The compounds such as 4g and 4h containing a n N-(4-bromo-2-methylphenyl)- or N-(4-bromo-3-methylphenyl)amino subst ituent exhibited the most potent antifungal activities.