2-amino-1,3,4-tiyadiazol türevlerinin halka siklizasyonu ile bazı yeni imidazo[ 2,1-b ][ 1,3,4 ] tiyadiazol türevlerinin sentezi ve karakterizasyonu
Küçük Resim Yok
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Karabük Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sentezlediğimiz imidazo[2,1-b][1,3,4]tiyadiazol bireşikleri ve onların türevlerinin bilimsel araştırmaya konu olmasının temel iki büyük nedeni vardır. Birinci neden anti kanserojen etkisinin olmasıdır. Bildiğimiz gibi kanser anormal hücrelerin kontrolsüz olarak bölündüğü ve yakın dokuları işgal ettiği hastalıktır. Bu hastalığın ortaya çıkma nedenlerine dair farklı varsayımlar bulunmaktadır. Bu hipotezlerden birine göre TGF? reseptörleri LOH (Loss of heterozygosity) (Heterozigotluk kaybı) veya mutasyon sonrası Epitelyal Mezankimal Geçişi desteklemesi sonucu kanser hücrelerinin metastazına neden olur. Kanserojen hücrelerin metastazını durdurabilmek için TGF? reseptörlerinin sinyal yolağını inhibe etmek gerekir. Bu reseptör üç temel kısımdan oluşmaktadır. Bunlar zarın hücre dışındaki kısmı, hücre zarı içerisinde kalan kısmı ve sitozoldeki kısımdır. TGF? reseptörünün hücre içerisindeki kısmı metastazı destekleyen sinyal yolağının başlangıç noktasıdır. TGF? reseptörünün bu kısmında ATP (Adenozin Tri fosfat) moleküllerindeki fosfat grupları TGF? reseptörüne transfer edilir ve böylece metastazın oluşumunu tetikleyen sinyalin ilk aşaması hayata geçirilmiş olur. İmidazo[2,1-b][1,3,4]tiyadiazol türevlerinin iskelesi ATP' ye benzediği için onlar ATP molekülleri yerine TGF? reseptörlerine bağlanarak burada oluşan fosforilasyon reaksiyonunu durdurur. Bu teorik bilgilere dayanarak biz imidazo[2,1-b][1,3,4]tiyadiazol birleşmelerinin yeni türevlerini sentezledik. İmidazo[2,1-b][1,3,4]tiyadiazol türevlerinin bilimsel açıdan dikkat çekmesinin ikinci büyük nedeni ise bu birleşiklerin antibakteriyal özelliklerinin olmasıdır. Bakterilerin antibakteriyal ilaçlara karşı direnç kazanması yeni sorunlara neden olmuştur. Bu nedenle yeni antibakteriyal ilaçlar tasarlamak olası pandemiyalardan korunmak için gereklidir Bu birleşiklerin antimikrobiyal etkilere sahip olması onların olası salgın hastalıklar sırasında dirençli bakterilere karşı kullanılabilmeleridir. Tüm bu teorik veriler dayanrak bu birleşiklerin anti kanserojen ve anti bakteriyal ilaç gibi kullanılabilir olması bu maddelerin önemini artırmaktadır. Bu çalışmamızda 23 adet yeni sübstitüe imidazo[2,1-b][1,3,4]tiyadiazol türevleri (4-13, 16-19, 22-26 ve 29-32) elde edilmiştir. Bu amaçla imidazo[2,1-b][1,3,4]tiyadiazol türevleri (4-13, 16-19, 22-26 ve 29-32) 2-amino-1,3,4-tiyadiazol türevlerinin (3, 15, 21 ve 28) çeşitli fenasilbromür türevleriyle ayrı ayrı reaksiyona sokulması ile orijinal olan 23 adet yeni imidazo[2,1-b][1,3,4]tiyadiazol bileşikleri orta-iyi verimlerle (59-77%) elde edilmiştir. Tüm sentezlenen bileşiklerin yapıları, IR, 1H-NMR, 13C-NMR, elemental analiz ve kütle spektroskopisi ile karakterize edildi ve ayrıca X-Ray kırılma analizi 6, 7, 16, 17, 19 ve 31 bileşikleri için kullanıldı.
The synthesized imidazo [2,1-b] [1,3,4] thiadiazole compounds and their derivatives are two major reasons for being subject to scientific research. The first reason is the anti-carcinogenic effect. As we know, cancer is a disorder in which abnormal cells divide uncontrollably and invade nearby tissues. There are different assumptions about the causes of this disease. According to one of these hypotheses, the TGF? receptors LOS (Loss of heterozygosity) or Epithelial–mesenchymal transition after mutation causes the metastasis of end-stage cancer cells. In order to stop the metastasis of carcinogenic cells it is necessary to inhibit the signaling pathway of TGF? Receptors. This receptor is composed of three basic parts. These are part of the membrane outside the cell, part inside the cell membrane and part inside the cytosol. The part of the TGF? receptor within the cell is the origin of the signal pathway that promotes metastasis. In this part of the TGF? receptor, the phosphate groups in the ATP (Adenosine Triphosphate) molecules are transferred to the TGF? receptor, so that the first stage of the signal that triggers the formation of metastasis is passed on. Since the imidazo [2,1-b] [1,3,4] thiadiazole derivatives are similar to ATP, they bind to TGF? receptors instead of ATP molecules, stopping the phosphorylation reaction that takes place here. Based on this theoretical knowledge, we have synthesized novel derivatives of imidazo [2,1-b] [1,3,4] thiadiazole compounds. The second major reason why the imidazo [2,1-b] [1,3,4] thiadiazole derivatives attract scientific attention is the antibacterial properties of these compounds. Bacterial resistance to antibacterial drugs has caused new problems. Therefore, designing new antibacterial medicines is necessary to protect against possible pandemics. These compounds have antimicrobial effects that they can be used against resistant bacteria during possible epidemic diseases. All these theoretical data suggest that these compounds can be used as anti-carcinogenic and anti-bacterial medicines, thus increasing the importance of these substances. In this study, 23 new substituted imidazo [2,1-b] [1,3,4] thiadiazole derivatives (4-13, 16-19, 22-26 and 29-32) were obtained. For this purpose, imidazo [2,1-b] [1,3,4] thiadiazole derivatives (4-13, 16-19, 22-26 and 29-32) 3, 15, 21 and 28) were reacted separately with various phenacylbromide derivatives to obtain 23 novel imidazo [2,1-b] [1,3,4] thiadiazole compounds which were originally obtained in moderate to good yields (59-77%). The structures of all synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, elemental analysis and mass spectroscopy and also X-Ray fracture analysis was used for compounds 6, 7, 16, 17, 19 and 31
The synthesized imidazo [2,1-b] [1,3,4] thiadiazole compounds and their derivatives are two major reasons for being subject to scientific research. The first reason is the anti-carcinogenic effect. As we know, cancer is a disorder in which abnormal cells divide uncontrollably and invade nearby tissues. There are different assumptions about the causes of this disease. According to one of these hypotheses, the TGF? receptors LOS (Loss of heterozygosity) or Epithelial–mesenchymal transition after mutation causes the metastasis of end-stage cancer cells. In order to stop the metastasis of carcinogenic cells it is necessary to inhibit the signaling pathway of TGF? Receptors. This receptor is composed of three basic parts. These are part of the membrane outside the cell, part inside the cell membrane and part inside the cytosol. The part of the TGF? receptor within the cell is the origin of the signal pathway that promotes metastasis. In this part of the TGF? receptor, the phosphate groups in the ATP (Adenosine Triphosphate) molecules are transferred to the TGF? receptor, so that the first stage of the signal that triggers the formation of metastasis is passed on. Since the imidazo [2,1-b] [1,3,4] thiadiazole derivatives are similar to ATP, they bind to TGF? receptors instead of ATP molecules, stopping the phosphorylation reaction that takes place here. Based on this theoretical knowledge, we have synthesized novel derivatives of imidazo [2,1-b] [1,3,4] thiadiazole compounds. The second major reason why the imidazo [2,1-b] [1,3,4] thiadiazole derivatives attract scientific attention is the antibacterial properties of these compounds. Bacterial resistance to antibacterial drugs has caused new problems. Therefore, designing new antibacterial medicines is necessary to protect against possible pandemics. These compounds have antimicrobial effects that they can be used against resistant bacteria during possible epidemic diseases. All these theoretical data suggest that these compounds can be used as anti-carcinogenic and anti-bacterial medicines, thus increasing the importance of these substances. In this study, 23 new substituted imidazo [2,1-b] [1,3,4] thiadiazole derivatives (4-13, 16-19, 22-26 and 29-32) were obtained. For this purpose, imidazo [2,1-b] [1,3,4] thiadiazole derivatives (4-13, 16-19, 22-26 and 29-32) 3, 15, 21 and 28) were reacted separately with various phenacylbromide derivatives to obtain 23 novel imidazo [2,1-b] [1,3,4] thiadiazole compounds which were originally obtained in moderate to good yields (59-77%). The structures of all synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, elemental analysis and mass spectroscopy and also X-Ray fracture analysis was used for compounds 6, 7, 16, 17, 19 and 31
Açıklama
Fen Bilimleri Enstitüsü, Kimya Ana Bilim Dalı
Anahtar Kelimeler
Kimya, Chemistry