Peptit içeren yeni sülfonamit türevleri sentezi
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Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Peptitler birçok biyolojik mekanizmayı düzenler ve bu özellik onları ilaç etken maddesi olma yolunda cazip moleküller haline getirir. Literatür taraması, sülfonamidlerin ve kısa peptit dizilerinin ayrı olarak geniş biyolojik aktiviteye sahip olduğunu göstermektedir. Düşük moleküler ağırlıklı peptitlerin biyolojik engelleri daha kolay geçtiği ve proteaz saldırılarına daha az duyarlı oldukları da bilinmektedir. Bu amaçla dipeptiler ile sülfonamit türevleri etkileştirilerek biyolojik sistemlere benzer muhtemel aktif bileşikler sentez edilmesi hedeflenmiştir. Bu konuda literatürde son derece sınırlı bir bilgi mevcuttur. Bu tez kapsamında aşağıda şemada özetlendiği gibi dipeptit içeren yeni sülfonamit türevleri hazırlanmıştır. Elde edilen tüm yeni bileşiklerin yapıları spektroskopik yöntemlerle (IR, NMR, MS) belirlenmiş ve bazı insan karbonik anhidraz enzimlerine (hCA I, hCA II, hCA IV, hCA IX ve hCA XII) karşı inhibisyon değerleri belirlenmiştir. Sentezlenen dipeptitlerin çoğunluğu karbonik anhidraz enzimlerini nanomolar seviyelerinde inhibe etmiştir. Bununla birlike alanin, fenilalanin, valin, lösin, izolösin ve metiyonin amimo asit içerenler en iyi karbonik anhidraz enzim inhibtör özelliği sergilemişlerdir.
Peptides regulate many biological mechanisms, which make them attractive molecules to become drug active substances. The literature review shows that the sulfonamides and short peptide sequences separately have broad biological activity. It is also known that low molecular weight peptides cross biological barriers more easily and they also less susceptible to protease attacks. However, it has disadvantages such as low bioavailability and poor stability. It is therefore important to replace the peptide moieties with high affinity non-peptide structures. For this purpose, it is aimed to synthesize possible active compounds similar to biological systems by the reaction of dipeptides and sulfonamide derivatives. There is very limited information on this subject in the literature. Within the scope of this thesis, new sulfonamide derivatives containing dipeptide were prepared as summarized in the scheme below. The structures of all new compounds were determined by spectroscopic methods (IR, NMR, MS) and their carbonic anhydrase inhibitory properties were determined against some human carbonic anhydrase enzymes (hCA I, hCA II, hCA IV, hCA IX and hCA XII). The majority of synthesized dipeptides inhibited carbonic anhydrase enzymes at nanomolar levels. However, those containing alanine, phenylalanine, valine, leucine, isoleucine and methionine amino acid exhibited the best carbonic anhydrase enzyme inhibitor properties.
Peptides regulate many biological mechanisms, which make them attractive molecules to become drug active substances. The literature review shows that the sulfonamides and short peptide sequences separately have broad biological activity. It is also known that low molecular weight peptides cross biological barriers more easily and they also less susceptible to protease attacks. However, it has disadvantages such as low bioavailability and poor stability. It is therefore important to replace the peptide moieties with high affinity non-peptide structures. For this purpose, it is aimed to synthesize possible active compounds similar to biological systems by the reaction of dipeptides and sulfonamide derivatives. There is very limited information on this subject in the literature. Within the scope of this thesis, new sulfonamide derivatives containing dipeptide were prepared as summarized in the scheme below. The structures of all new compounds were determined by spectroscopic methods (IR, NMR, MS) and their carbonic anhydrase inhibitory properties were determined against some human carbonic anhydrase enzymes (hCA I, hCA II, hCA IV, hCA IX and hCA XII). The majority of synthesized dipeptides inhibited carbonic anhydrase enzymes at nanomolar levels. However, those containing alanine, phenylalanine, valine, leucine, isoleucine and methionine amino acid exhibited the best carbonic anhydrase enzyme inhibitor properties.
Açıklama
Anahtar Kelimeler
Kimya, Chemistry
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Buğday, N. (2019). Peptit içeren yeni sülfonamit türevleri sentezi. Yayınlanmış Doktora Tezi, İnönü Üniversitesi.
