Synthesis and antimicrobial activity of some 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione deriv atives

Bazı 3,5-disübstitüe-tetrahidro-2H-1,3,5-tiyadiazin-2-tiyontürevlerinin sentezi ve antimikrobiyal aktivitesi

Özet

Uygun ve genel tek-kap yöntemle bir seri yeni 3,5-disübstitüe-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon (THTT) türevlerinin (4a-g) sentezi yapılmis ve bileşiklerin in vitro antibakteriyel ve antifungal etkileri mikrodilüsyon yöntemi kullanrfarak, ampisilin ve flukonazol ile karsilaştinlarak incelenmiştir. 3-Fenil-5-(l-feniletil)-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon’un (4a) Staphylococcus aureus’a ve 3-fenil-5-hidroksi-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon’un (4g) Enterococcus faecalis’e karsi 4 ve 16 pLg/mL MİK değerleriyle aktif olduğu bulunmuştur. 3-Fenil-5-(l-feniletil)-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon’un (4a) Candida krusei (MİK: 8 pLg/mL) ve C. parapsilosis’e (MİK: 4 pLg/mL) karsi antifungal aktivitesinin ftukonazolden daha yüksek olduğu (MİK: 64 pLg/mL ve 8 pLg/mL) gorülmustür. 3-Fenil-5-(l-feniletil)-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon (4a) C. albicans’a karsi 4 pLg/mL konsantrasyonda antifungal aktivite göstermiştir. 3-(l-Feniletil-5-[a-(izobutil)karboksimetil]-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon (4b) ve 3-benzil-5-karboksietil-tetrahidro-2H-l,3,5-tiyadiazin-2-tiyon’un (4c) C. krusei’ye karsi antifungal aktivitesinin flukonazole benzer olduğu bulunmuştur (MİK: 64 μg/mL).

Abstract

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 3-phenyl-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-1,3,5-thiadiazine-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-1,3,5-thiadiazine-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).