The synthesis of 6-(N-arylamino)-7-chloro-5,8-quinolinedione derivatives for evaluation of antifungal activities

Abstract

A series of 6-(N-arylamino)-7-chloro-5,8-quinolinedione derivatives was newly synthesized for the evaluation of antifungal activities. 5-Amino-8-hydroxy-quinoline (II) was treated with KClO3 in HCl to give 6,7-dichloro-5,8-quinolinediones (III). 6-(N-Arylamino)-7-chloro-5,8-quinolinediones 1-12 were prepared by regioselective nucleophilic substitution of III with arylamines. In the presence of CeCl3, the N-arylamino groups were introduced at the 6-position of 5,8-quinolinedione ring by the regioselective substitution. These derivatives 1-12 were tested for antifungal and also antibacterial activities, in vitro, against Candida albicans, Aspergillus niger, Tricophyton mentagrophytes, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. The MIC values were determined by the two-fold agar/streak dilution method. Newly obtained 6-(N-arylamino)-7-chloro-5,8-quinolinedione derivatives showed potent antifungal and antibacterial activities. Among these derivatives, 1, 3, 5, 7, 8 and 9 showed more potent antifungal activities than fluconazole and griseofulvin. Also most of derivatives were found to be more active than ampicillin against gram-positive bacteria. 1 and 7 showed the very potent antifungal activities. 1 was the most effective in preventing the growth of Candida albicans, Aspergillus niger, Tricophyton mentagrophytes, Bacillus subtilis and Staphylococcus aureus at MIC 1.6 μg/ml.