İBUPROFEN TÜREVİ SPİROTHİAZOLİDİNONLARIN SENTEZİ, KARAKTERİZASYONU VE KOLİNESTERAZ İNHİBİTÖR ETKİLERİ

Öz

Amaç: Alzheimer hastalığına karşı potansiyel asetilkolinesteraz (AChE) ve butirilkolinesteraz (BuChE) inhibitörleri olarak bir seri yeni spirotiyazolidinon türevi tasarlanmış, sentezlenmiş ve inhibisyon etkileri değerlendirilmiştir. Gereç ve Yöntem: Bu çalışmadan kazanılan yeni spiro bileşikler tek kap yöntemi ile sentez edilmiştir. Bileşiklerin kimyasal yapılarını aydınlatmak için IR, 1H NMR, 13C NMR, LC-MS ve elementel analiz yöntemleri kullanılmıştır. Bileşiklerin (4a-e ve 5a-e), AChE ve BuChE enzimleri üzerindeki inhibisyon etkileri galantamin referans olarak kullanılarak Ellman yöntemine göre analiz edilmiştir. Sonuç ve Tartışma: İnhibisyon sonuçlarına göre, en umut verici bileşik AChE'ye karşı IC50 değeri 39.53±1.94 µM olan 4e ve BuChE'ye karşı IC50 değeri 95.97±1.79 µM olan 4b bileşikleri olarak kaydedilmiştir.

Anahtar Kelimeler

• Asetilkolinesteraz
• butirilkolinesteraz
• ibuprofen
• sentez
• spirotiyazolidinon

SYNTHESIS, CHARACTERIZATION AND CHOLINESTERASE INHIBITORY EFFECTS OF IBUPROFEN-BASED SPIROTHIAZOLIDINONES

Öz

Objective: A novel class of spirothiazolidinone derivatives were designed, synthesized, and assessed as possible acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors for Alzheimer's disease therapy. Material and Method: In this study, novel spirocyclic compounds were synthesized by one-pot reaction. IR, 1H NMR, 13C NMR, LC-MS and elemental analysis techniques have all been used to clarify the chemical structures of the compounds. AChE and BuChE inhibitory effects of compounds (4a-e and, 5a-e) were assayed according to Ellman’s method using galantamine as reference. Result and Discussion: According to the inhibition data, compound 4e demonstrated the most promising activity against AChE, with an IC50 value of 39.53±1.94 µM, while compound 4b exhibited the most potential against BuChE, with an IC50 value of 95.97±1.79 µM.

Anahtar Kelimeler

• Acetylcholinesterase
• butyrylcholinesterase
• ibuprofen
• spirothiazolidinone
• synthesis

Kaynakça

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