Synthesis and in vitro antifungal and cytotoxicity evaluation of substituted 4,5-dihydronaphtho[1,2-d][1,2,3]thia(or selena)diazoles

Abstract Unsubstituted 4,5-dihydronaphtho[1,2- d ][1,2,3]thia (or selena)diazoles ( 2a , 2b ), prepared from the semicarbazone ( 1a ), were nitrated using fuming nitric acid at 0 °C to yield various mono-nitrated dihydronaphthalenes ( 3a – 3e ). Related sulfamoyl derivatives ( 4a , 4b ) were prepared using chlorosulfonic acid, followed by the addition of ammonia solution. Synthesis of 6,9-dimethoxy-4,5-dihydronaphtho[1,2- d ][1,2,3]thiadiazole derivative ( 2c ) was performed using 5,8-dimethoxy-α-tetralone semicarbazone ( 1b ) and thionylchloride at low temperature. At 10 ppm concentration, all compounds showed low toxicity (higher than 80% survival) on brine shrimps, while at 100 ppm concentration compounds 2d , 3d , and 4b exhibited toxicity (less than 60% survival) . Compounds 3a , 3e , and especially 4a showed significant antifungal activity against Cryptococcus neoformans . Compound 4a , while being the most active antifungal agent in this series, possessed low toxicity.