Enflamatuar bağırsak hastalığı tedavisi için semisentetik fitokimyasal yapı geliştirilmesi
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Dosyalar
Tarih
2023
Yazarlar
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Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Enflamatuar bağırsak hastalığı, bireylerin yaşamının her yönünü etkileyen, sağlık sistemi ve toplum için önemli maliyetlere neden olan kronik, engelleyici gastrointestinal bozukluklardır. Yeni epidemiyolojik veriler, enflamatuar bağırsak hastalığı insidansının ve prevalansının giderek arttığını göstermektedir. Bu durum tıbbi tedavi ve hastalık yönetiminin son yıllarda önemli ölçüde değişip gelişmesine sebep olmuştur. Enflamatuar bağırsak hastalığı tedavisinde kullanılan aminosalisilik asit türevleri, kortikosteroidler ve immünosupresanlar gibi klasik ilaçların yan etki profilleri ve kesin bir çözüm sağlayamayışı daha az toksisiteye sahip antienflamatuvar özellikteki doğal bileşiklere yönelimi tetiklemiştir. Bu çalışmada, enflamatuar bağırsak hastalığı tedavisi için glikozamin ve gallik asit türevleri kullanılarak amidifikasyon reaksiyonu sonucunda sübstitüe N-glikozbenzamid türevleri kimyasal yöntemlerle sentezlenmiştir. Elde edilen bileşikler saflaştırıldıktan sonra, proton nükleer manyetik rezonans gibi çeşitli spektroskopik yöntemlerle yapısı aydınlatılmış ve elde edilen bileşiklerin antienflamatuar fonksiyonunun etkileyebileceği spesifik mekanizmalara yanıtı in vitro enflamatuar bağırsak hastalığı modelinde değerlendirilmiştir. Sentezlediğimiz özgün bileşiklerden ikisinin hidrojen peroksit uyarımı varlığındaki nitrik oksit seviyelerini önemli düzeyde baskılayarak antienflamatuar etki gösterdiği ayrıca tümör nekroz faktör alfa ve interlökin 6 gibi proenflamatuar sitokinlerin seviyelerini de baskıladığı tespit edilmiştir.
Inflammatory bowel disease are chronic, disabling gastrointestinal disorders that affect every aspect of individual's lives and cause significant costs to the healthcare system and society. Recent epidemiological data indicate that the incidence and prevalence of inflammatory bowel disease is increasing. This has led to a significant impact on medical treatment and disease management in recent years. Side effect profiles of classical drugs such as aminosalicylic acid derivatives, corticosteroids and immunosuppressants used in the treatment of inflammatory bowel disease and the inability to provide a definitive solution have triggered the tendency to natural compounds with antiinflammatory properties with less toxicity. In this study, substituted N-glucosbenzamide derivatives were synthesized by chemical methods as a result of amidification reaction by using glucosamine and gallic acid derivatives for the treatment of inflammatory bowel disease. After the obtained compounds were purified, their structures were elucidated by various spectroscopic methods such as proton nuclear magnetic resonance, and the response of the obtained compounds to specific mechanisms that could affect the anti-inflammatory function was evaluated in an in vitro inflammatory bowel disease model. It was determined that two of the unique compounds we synthesized showed anti-inflammatory effects by significantly suppressing nitric oxide levels in the presence of hydrogen peroxide stimulation, and also suppressed the levels of proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 6.
Inflammatory bowel disease are chronic, disabling gastrointestinal disorders that affect every aspect of individual's lives and cause significant costs to the healthcare system and society. Recent epidemiological data indicate that the incidence and prevalence of inflammatory bowel disease is increasing. This has led to a significant impact on medical treatment and disease management in recent years. Side effect profiles of classical drugs such as aminosalicylic acid derivatives, corticosteroids and immunosuppressants used in the treatment of inflammatory bowel disease and the inability to provide a definitive solution have triggered the tendency to natural compounds with antiinflammatory properties with less toxicity. In this study, substituted N-glucosbenzamide derivatives were synthesized by chemical methods as a result of amidification reaction by using glucosamine and gallic acid derivatives for the treatment of inflammatory bowel disease. After the obtained compounds were purified, their structures were elucidated by various spectroscopic methods such as proton nuclear magnetic resonance, and the response of the obtained compounds to specific mechanisms that could affect the anti-inflammatory function was evaluated in an in vitro inflammatory bowel disease model. It was determined that two of the unique compounds we synthesized showed anti-inflammatory effects by significantly suppressing nitric oxide levels in the presence of hydrogen peroxide stimulation, and also suppressed the levels of proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 6.
Açıklama
Anahtar Kelimeler
Enflamasyon, Enflamatuar bağırsak hastalığı, Fitokimyasal, Enflammation, Enflammatory bowel disease, Phytochemical
