Publication: 5-(4-Aminofenil)-2-Sübstitüeamino-1,3,4-Tiyadiazol bileşiklerinden türeyen Sübstitüe ürelerin sentezi ve yapılarının aydınlatılması
Abstract
1.ÖZET Bu araştırmada, antimikrobiyal ve sitotoksik etkilerinin taranması amacı ile N-5-(4-aminofenil)-2-alkil/ arilamino-1-3,4-tiyadiazol-N'-alkil/ aril)üre türevi bi-leşikler sentezlenmiştir. Araştırmanın birinci kısmında, benzokainin hidrazin hidrat ile reaksiyona sokularak 4-(benzoilamino)benzoilhidrazin kazanılmış, bu bileşiğin etil, siklohekzil, fenil, fenetil ve 4-klorofenil isotiyosiyanatlara katımı ile 1-[4-(benzoilamino)benzoil]-4-alkil/ ariltiyosemikarbazidler (3a-e) sentezlenmiştir. 3a-e’den hareketle, 2-(4-aminofenil)-5-alkil/ arilamino-1,3,4-tiyadiazoller (4a-e) anabilim dalımız tarafından modifiye edilen yeni bir yöntem ile elde edilmişlerdir. Araştırmanın ikinci bölümünde, aromatik primer aminler diklorometanlı ortamda butil, t-butil, 4-klorofenil, 2-kloro-6-metilfenil ve 4-triflorometilfenil isosiyanatlara katımları ile onüç adet orijinal üre bileşiği (5a-e) kazanılmıştır. Sentez edilen bileşiklerin saflıkları ince tabaka kromatografisi ile kontrol edildikten sonra yapıları, elementel analiz (C, H, N ve S), UV, IR, 1H-NMR ve kütle spektroskopik yöntemleri kullanılarak aydınlatılmıştır. Bileşiklerin antimikrobiyal etkileri belirlenmiş bazı suşlara karşı Minimum İnhibitör Konsantrasyon (MİK) değerleri mikrodilüsyon yöntemiyle saptanmıştır. Bileşiklerimiz kullanılan standartlar ile kıyaslandıklarında kayda değer antimikrobiyal etki göstermedikleri tespit edilmiştir. Bileşiklerin sitotoksik etlileri HeLa (ATCC CCL-2) hücre hattı kullanılarak MTT [3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür] yöntemine [Cell proliferation Kit I (MTT) Roche-Germany] göre test edilmiştir. Bileşikler içerisinde en yüksek sitotoksik etki N-[4-(2-siklohegzilamino-1,3,4-tiyadiazol-5-il)fenil]-N'-(4-kloro-fenil)üre (5b-III ) için % 82 olarak tespit edilmiştir. Anahtar Sözcükler: Üre, 1,3,4-tiyadiazol, sentez, antimikrobiyal etki, sitotoksik etki 2.
SYNTHESIS OF UREAS DERIVED FROM 5-(4-AMİNOPHENYL)-2-SUBSTITUEAMINO-1,3,4-THIADIAZOLE AND CHARACTERİZED STRUCTURES In thisresearch, in order to screen antimicrobial and cyctotoxic activities, substituted N-[4-(2-aryl/ alkylamino–1,3,4-thiadiazole–5-yl)phenyl]-N'-(aryl/ alkyl)-ureas were synhesized. In the first part of research, benzocaine was reacted with hydrazine hydrate to prepare 4-(benzoylamino)benzoylhydrazine. 1-[4-(Benzoylamino)benzoyl]-4-alkyl/ arylthiosemikarbazides were then synthesized by the addition of ethyl, cyclohexyl, phenyl, phenethyl and 4-chlorophenyl isothiocyanates to added 4-(benzoylamino)benzoylhydrazine. From (3a-e), 2-(4-aminophenyl-5-alkyl/ arylamino-1,3,4-thiadiazoles (4a-e) were synthesized by using a new method which was modified by our department. In the second part, N-aryl/ alkyl-N-[4-(5-alkyl/ arylamino-1,3,4-thiadiazole-2-yl)phenyl]ureas were ob-tained from the addition of aromatic primary amine to butyl, t-butyl,4-chlorophenyl, 2-chloro-6-methyl, 4-trifloromethylphenyl isocyanates in dry dichloromethane. Purity of the synthesized compounds were controlled with thin layer chromatographic methods. The structures of the compounds synthesized were confirmed by elementel analysis (C, H, N, S), UV, IR, 1H-NMR methods. Antimycobacterial activites of the compounds synthesized were tested by some strains were determined and the Minium Inhibitor Concetrarion ( MIC) was defined as the lowest concentration of compound giving complete inhibition of visible growth. Compared with the standard compounds used were found not show significant antimicrobial effects.Cyctoxicity of these compounds were evaluated by using HeLa (ATCC CCL-2) cell line according to procedures of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] Assay [Cell proliferation Kit I (MTT) Roche-Germany]. The highest inhibition was confirmed as 82% for the compound N-[4-(2-cyclohegzylamino-1,3,4-thiadiazole-5-yl)phenyl]-N'-(4-chloro-phenyl)urea [5b-III]. Key words: Urea, 1,3,4-thiadiazole, synthesis, antimicrobial, cytotoxic activity.
SYNTHESIS OF UREAS DERIVED FROM 5-(4-AMİNOPHENYL)-2-SUBSTITUEAMINO-1,3,4-THIADIAZOLE AND CHARACTERİZED STRUCTURES In thisresearch, in order to screen antimicrobial and cyctotoxic activities, substituted N-[4-(2-aryl/ alkylamino–1,3,4-thiadiazole–5-yl)phenyl]-N'-(aryl/ alkyl)-ureas were synhesized. In the first part of research, benzocaine was reacted with hydrazine hydrate to prepare 4-(benzoylamino)benzoylhydrazine. 1-[4-(Benzoylamino)benzoyl]-4-alkyl/ arylthiosemikarbazides were then synthesized by the addition of ethyl, cyclohexyl, phenyl, phenethyl and 4-chlorophenyl isothiocyanates to added 4-(benzoylamino)benzoylhydrazine. From (3a-e), 2-(4-aminophenyl-5-alkyl/ arylamino-1,3,4-thiadiazoles (4a-e) were synthesized by using a new method which was modified by our department. In the second part, N-aryl/ alkyl-N-[4-(5-alkyl/ arylamino-1,3,4-thiadiazole-2-yl)phenyl]ureas were ob-tained from the addition of aromatic primary amine to butyl, t-butyl,4-chlorophenyl, 2-chloro-6-methyl, 4-trifloromethylphenyl isocyanates in dry dichloromethane. Purity of the synthesized compounds were controlled with thin layer chromatographic methods. The structures of the compounds synthesized were confirmed by elementel analysis (C, H, N, S), UV, IR, 1H-NMR methods. Antimycobacterial activites of the compounds synthesized were tested by some strains were determined and the Minium Inhibitor Concetrarion ( MIC) was defined as the lowest concentration of compound giving complete inhibition of visible growth. Compared with the standard compounds used were found not show significant antimicrobial effects.Cyctoxicity of these compounds were evaluated by using HeLa (ATCC CCL-2) cell line according to procedures of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] Assay [Cell proliferation Kit I (MTT) Roche-Germany]. The highest inhibition was confirmed as 82% for the compound N-[4-(2-cyclohegzylamino-1,3,4-thiadiazole-5-yl)phenyl]-N'-(4-chloro-phenyl)urea [5b-III]. Key words: Urea, 1,3,4-thiadiazole, synthesis, antimicrobial, cytotoxic activity.