Benzotiyazol ve imidazo [ 2,1-b ] [ 1,3,4 ] tiyadiazol halkasını birlikte içeren bileşiklerin sentezi, karakterizasyonu ve biyolojik aktivitelerinin incelenmesi
Küçük Resim Yok
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Karabük Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Benzotiyazol, imidazol ve tiyadiazol halkası içeren bileşikler sahip oldukları biyolojik aktivite ile heterosiklik kimyada önemli rol oynamaktadırlar. Son yıllarda yapılan çalışmalar imidazo[2,1-b][1,3,4]tiyadiazol türevlerinin antimikrobiyal, antifungal, antikanser, antitüberküloz, antienflamatuvar, antikonvülzan, analjezik, anestetik, antihiperlipidemik ve diüretik gibi birçok biyolojik aktiviteye sahip olduğunu göstermiştir. İmidazo[2,1-b][1,3,4]tiyadiazol türevi bileşikler üzerine kimya, tıp ve eczacılık alanında pek çok çalışma yapılmış, bu bileşikler ilaç sektöründe ise ilgi çekici bir alan haline gelmiştir. Bu çalışmanın ana amacı, biyolojik aktiviteye sahip imidazo[2,1-b][1,3,4]tiyadiazol türevi içeren yeni bileşikler (5-24) sentezlemek, çeşitli spektroskopik yöntemlerle karakterize etmek ve biyolojik aktivitelerini incelemektir. Çalışmanın ilk bölümünde benzo[d]tiyazol-2-tiyol/ol bileşiklerinin (1a,b) klorasetonitril ile nükleofilik yer değiştirme reaksiyonu sonucunda (benzo[d]tiyazol-2-iltiyo/oksi)asetonitril (3a,b) bileşikleri %82 ve %87 oranlarında sentezlenmiştir. Daha sonra (benzo[d]tiyazol-2-iltiyo/oksi)asetonitril bileşiklerinin (3a,b) tiyosemikarbazit ile reaksiyonu sonucu halka kapanması meydana gelmiş ve 2-amino-1,3,4-tiyadiazol türevleri (4a,b) elde edilmiştir. Son kısımda ise hedef bileşikler olan imidazo[2,1-b][1,3,4]tiyadiazol türevi 20 yeni bileşik (5-24), (4a,b) bileşiklerinin fenasil bromür türevleriyle olan reaksiyonlarından orta-iyi verimlerle (53-73%) elde edilmiştir. Sentezlenen bileşiklerin yapısı IR, 1H-NMR, 13C-NMR ve MS kullanılarak karakterize edilmiştir. Çalışmanın son bölümünde ise sentezlenen bileşiklerin antileishmanial ve antibakteriyel biyolojik aktivite çalışmaları yapılmıştır. Çalışmamızda sentezlenmiş olan bileşiklerin antileishmanial ve antibakteriyel aktivitele çalışmaları 96 kuyucuklu mikroplarda sıvı mikrodilüsyon alamar mavisi yöntemi kullanılarak araştırılmıştır. Çalışmada antileishmanial aktivite bakılan bileşiklerden 8 numaralı bileşiğin (MİK = 10 000 ?g/mL) en çok etkili olduğu görülmüştür. Ayrıca 7 ve 17 numaralı bileşiklerin (MİK = 20 000 ?g/mL) de çalışılan en yüksek konsantrasyonda etkili oldukları belirlenmiştir. Antibakteriyel aktivite çalışmasında ise 4b ve 7 numaralı bileşiklerin Escherichia coli bakteri türüne karşı (MİK = 625 ?g/mL) en etkili bileşikler olduğu gözlenmiştir. Ayrıca 4b numaralı bileşiğin Yersinia enterocolitica bakteri türüne karşı (MİK = 1 250 ?g/mL) en etkili bileşik olduğu gözlenmiştir. Anahtar Sözcükler : Benzotiyazol, 1,3,4-Tiyadiazol, İmidazo[2,1-b][1,3,4] tiyadiazol, Antileishmanial aktivite, Antibakteriyel aktivite.
Compounds containing the benzothiazole, imidazole and thiadiazole ring play an important role in the heterocyclic chemistry by their biological activity. Recent studies have shown that imidazo[2,1-b][1,3,4]thiadiazole derivatives have biological activity such as antimicrobial, antifungal, anticancer, antituberculosis, anti-inflammatory, anticonvulsan, analgesic, anaesthetic, antihyperlipidemic and diuretic. Many studies on imidazo[2,1-b][1,3,4]thiadiazole derivative compounds have been made in chemistry, medicine and pharmacy, and these compounds have become an interesting field in the pharmaceutical sector. The main aim of this study is to synthesize new compounds (5-24) containing imidazo[2,1-b][1,3,4]thiadiazole derivatives with biological activity, characterize them by various spectroscopic methods and examine their biological activities. In the first part of the study, as a result of the nucleophilic substitution reaction of benzo[d]thiazole-2-thiol/ol compounds (1a,b) with chloroacetonitrile, (benzo[d]thiazol-2-ylthio / oxy) acetonitrile (3a,b) compounds were synthesized at 82% and 87%. After that, following the reaction of the (benzo[d]thiazol-2-ylthio/oxy)acetonitrile compound (3a,b) with thiosemicarbazide, a ring closure occurred and 2-amino-1,3,4-thiadiazole derivatives (4a,b) were obtained. In the last part, imidazo[2,1-b][1,3,4]thiadiazole derivatives 20 new compounds (5-24), which are the target compounds were obtained intermediate-good yields (53-73%) from the reactions of (4a,b) compounds with the phenacyl bromide derivatives. The structure of the synthesized compounds were characterized using IR, 1H-NMR, 13C-NMR and MS. In the last part of the study, antileishmanial and antibacterial biological activity studies of the synthesized compounds were carried out. In our study, the antileishmanial and antibacterial activity of the synthesized compounds was investigated using liquid microdilution alamar blue method in 96-well microspheres. The compound 8 (MIC = 10 000 ?g/mL) was found to be the most effective from the compounds tested for antileishmanial activity. It has also been determined that compounds 7 and 17 (MIC = 20 000 ?g/mL) are effective at the highest concentration tested. Compounds 4b and 7 were the most effective against Escherichia coli bacteria (MIC = 625 ?g/mL) in the study of antibacterial activity. It was also observed that compound 4b was the most effective against Yersinia enterocolitica bacteria (MIC = 1 250 ?g/mL). Key Words : Benzothiazole, 1,3,4-Thiadiazole, Imidazo[2,1-b][1,3,4]thiadiazole Antileishmanial activity , Antibacterial activity.
Compounds containing the benzothiazole, imidazole and thiadiazole ring play an important role in the heterocyclic chemistry by their biological activity. Recent studies have shown that imidazo[2,1-b][1,3,4]thiadiazole derivatives have biological activity such as antimicrobial, antifungal, anticancer, antituberculosis, anti-inflammatory, anticonvulsan, analgesic, anaesthetic, antihyperlipidemic and diuretic. Many studies on imidazo[2,1-b][1,3,4]thiadiazole derivative compounds have been made in chemistry, medicine and pharmacy, and these compounds have become an interesting field in the pharmaceutical sector. The main aim of this study is to synthesize new compounds (5-24) containing imidazo[2,1-b][1,3,4]thiadiazole derivatives with biological activity, characterize them by various spectroscopic methods and examine their biological activities. In the first part of the study, as a result of the nucleophilic substitution reaction of benzo[d]thiazole-2-thiol/ol compounds (1a,b) with chloroacetonitrile, (benzo[d]thiazol-2-ylthio / oxy) acetonitrile (3a,b) compounds were synthesized at 82% and 87%. After that, following the reaction of the (benzo[d]thiazol-2-ylthio/oxy)acetonitrile compound (3a,b) with thiosemicarbazide, a ring closure occurred and 2-amino-1,3,4-thiadiazole derivatives (4a,b) were obtained. In the last part, imidazo[2,1-b][1,3,4]thiadiazole derivatives 20 new compounds (5-24), which are the target compounds were obtained intermediate-good yields (53-73%) from the reactions of (4a,b) compounds with the phenacyl bromide derivatives. The structure of the synthesized compounds were characterized using IR, 1H-NMR, 13C-NMR and MS. In the last part of the study, antileishmanial and antibacterial biological activity studies of the synthesized compounds were carried out. In our study, the antileishmanial and antibacterial activity of the synthesized compounds was investigated using liquid microdilution alamar blue method in 96-well microspheres. The compound 8 (MIC = 10 000 ?g/mL) was found to be the most effective from the compounds tested for antileishmanial activity. It has also been determined that compounds 7 and 17 (MIC = 20 000 ?g/mL) are effective at the highest concentration tested. Compounds 4b and 7 were the most effective against Escherichia coli bacteria (MIC = 625 ?g/mL) in the study of antibacterial activity. It was also observed that compound 4b was the most effective against Yersinia enterocolitica bacteria (MIC = 1 250 ?g/mL). Key Words : Benzothiazole, 1,3,4-Thiadiazole, Imidazo[2,1-b][1,3,4]thiadiazole Antileishmanial activity , Antibacterial activity.
Açıklama
Fen Bilimleri Enstitüsü, Kimya Ana Bilim Dalı
Anahtar Kelimeler
Kimya, Chemistry
