Original article SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME 3,5-DISUBSTITUTED-TETRAHYDRO-2H-1,3,5-THIADIAZINE- 2-THIONE DERIVATIVES

A series of new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives (4a-g) were prepared using a convenient and general one-pot procedure and evaluated for their in vitro antibacterial and antifungal activities by using the microdilution method in comparison with ampicillin and fluconazole. 3-Phenyl-5-(1-phenylethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (4a) and 3phenyl-5-hydroxy-tetrahydro-2H-1,3,5-thiadiazine-2-thione (4g) were found to be active against Staphylococcus aureus and Enterococcus faecalis with MIC values of 4 and 16 µg/mL, respectively. The antifungal activity of 3-phenyl-5-(1 -phenylethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (4a) against Candida krusei and C. parapsilosis appeared greater than that of fluconazole (MIC: 64 µg/mL and 8 µg/mL) with MIC of 8 and 4 µg/mL, respectively. 3-Phenyl-5-(1-phenylethyl)-tetrahydro-2H-1,3,5thiadiazine-2-thione (4a) also exhibited antifungal activity against C. albicans with a MIC of 4 µg/mL. The antifungal activity of 3-(1-phenylethyl-5-[α-(isobutyl)carboxymethyl]-tetrahydro-2H-1,3,5thiadiazine-2-thione (4b) and 3-benzyl-5-carboxyethyl-tetrahydro-2H-1,3,5-thiadiazine-2-thione (4c) against C. krusei were found to be similar to that of fluconazole (MIC: 64 µg/mL).