Synthesis and in vitro antifungal and cytotoxicity evaluation of substituted 4,5-dihydronaphtho[1,2-d][1,2,3]thia(or selena)diazoles.
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 degrees 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-alpha-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.
Jalilian
A R
AR
Cyclotron Department, Nuclear Research Center for Agriculture and Medicine, P.O.Box 31585-4395, Karaj, Iran.
Sattari
S
S
Bineshmarvasti
M
M
Daneshtalab
M
M
Shafiee
Abbas
A
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity*; D001156:Artemia / Q000187:drug effects / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity*
D000935:Antifungal Agents; D013830:Thiadiazoles