Asetilkolinesteraz inhibitörleri olarak imidazopiridin türevleri üzerine çalışmalar
Amaç: Bu çalışmada, imidazo[1,2-a]piridinin bazı hidrazid türevlerinin sentezlenmesi ve antikolinesteraz aktivitelerinin araştırılması amaçlandı. Yöntem: İmidazo[1,2-a]piridin-2-karboksilik asid hidrazidi ile çeşitli benzaldehit türevlerinin reaksiyonu ile hedef bileşikler olan N-(benziliden)imidazo[1,2-a]piridin-2-karboksilik asid hidrazid türevlerine ulaşıldı. Bileşiklerin kimyasal yapıları, IR, 1H-NMR ve FAB+-MS spektral verileri ve elementel analiz verileri ile aydınlatıldı. Modifiye edilmiş Ellman spektrofotometrik metodu kullanılarak, elde edilen tüm bileşiklerin asetilkolinesteraz (AChE) inhibisyonları incelendi.Bulgular: Donepezil (IC50=0.058±0.002 μM) ile kıyaslandığında, sentezlenen bileşiklerin üç tanesinin (2, 3 ve 4), IC50 değerleri sırasıyla 74.42±4.29, 43.26±7.28 ve 18.29±2.31 μM olarak ölçülmüş ve AChE üzerinde ümit verici inhibisyonları gözlenmiştir.Sonuçlar: Fenil halkası üzerindeki halojen sübstitisyonunun, antikolinesteraz etki üzerinde önemli katkısı vardır.
Anahtar Kelimeler:
İmidazo[1, 2-a]piridin, hidrazon, kolinesteraz inhibitörleri
Studies on imidazopyridine derivatives as acetylcholinesterase inhibitors
Objective: In this study we aimed to synthesize some hydrazide derivatives of imidazo[1,2-a]pyridine and to evaluate their anti-cholinesterase activities. Method: The reaction of imidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave N-(benzylidene)imidazo[1,2-a]pyridine-2-carboxylic acid hydrazide derivatives. The chemical structures of the compounds were elucidated by IR, 1H-NMR, FAB+-MS spectral data and elemental analysis. In the pharmacological study, anti-cholinesterase activities of these compounds have been evaluated by using modified Ellman’s spectrophotometric method.Results: Three of the synthesized compounds (2, 3 and 4) can be identified as promising anticholinesterase agents due to their inhibitory effect on AChE with IC50 value of 74.42±4.29, 43.26±7.28 and 18.29±2.31 μM, respectively when compared with Donepezil (IC50=0.058±0.002 μM).Conclusion: The halogen substitutions on phenyl ring have a crucial influence on anticholinesterase activity.
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- Yayın Aralığı: Yılda 4 Sayı
- Başlangıç: 2011
- Yayıncı: Marmara Üniversitesi
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Asetilkolinesteraz inhibitörleri olarak imidazopiridin türevleri üzerine çalışmalar
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