Antikolinerjik etkili nitrofuranlar: Alzheimer hastalığının tedavisine in vitro yaklaşım

Öz

Demansın önde gelen nedenlerinden biri olan Alzheimer hastalığı (AD), bilişsel işlevi ciddi şekilde etkiler ve asetilkolinin tükenmesi patogenezinde önemli bir faktördür. Bu çalışma, kapsamlı in vitro yaklaşımlar kullanarak nitrofuran analoğu olan nitrofurantoinin kolinesterazlar (ChE'ler) üzerindeki inhibitör potansiyelini araştırmaktadır. Bulgularımız, nitrofurantoinin asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BChE) üzerinde farklı inhibisyon gösterdiğini, AChE için 6,77 ± 0,56 μM ve BChE için 9,48 ± 0,69 μM inhibisyon sabitleri (KI)’ne sahip olduğunu göstermektedir. Bu değerler, referans ilaç takrinin KI değerlerinden (AChE için 0,17 ± 0,01 μM ve BChE için 0,13 ± 0,01 μM) daha az etkili olsa da, dikkate değer bir antikolinerjik kapasiteye işaret etmektedir. Bu çalışma, enzim inhibisyon dinamiklerine dair ayrıntılı içgörüler sağlayarak, nitrofuran türevlerinin AD'nin terapötik manzarasında optimize edilmesi için temel oluşturmaktadır. Bu bulguların çıkarımları, farmakolojik gelişmelerin daha geniş bağlamına uzanmakta ve nörodejeneratif hastalıkların yönetiminde hedeflenen enzim inhibisyonunun önemini vurgulamaktadır. Bu sonuçlara dayanarak yapılacak gelecekteki araştırmalar, daha etkili tedavilerin geliştirilmesine, AD'den etkilenen bireylerin yaşam kalitesinin artırılmasına ve klinik müdahale için yeni yollar sunulmasına yol açabilir.

Anahtar Kelimeler

• Asetilkolinesteraz
• Bütirilkolinesteraz
• Alzheimer hastalığı
• Nitrofuran türevi
• Enzim-ligand etkileşimleri

Nitrofurantoin with Anticholinergic Effect: A Different in Vitro Approach to Alzheimer's Disease

Öz

Alzheimer's disease (AD), a leading cause of dementia, severely affects cognitive function, with the depletion of acetylcholine being a pivotal factor in its pathogenesis. This study delves into the inhibitory potential of the nitrofuran analogue, nitrofurantoin on cholinesterases (ChEs) using comprehensive in vitro approaches. Our findings indicate that nitrofurantoin exhibits differential inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants (KI) of 6.77 ± 0.56 μM for AChE and 9.48 ± 0.69 μM for BChE. These values, although less potent than those of the reference drug tacrine (KIs of 0.17 ± 0.01 μM for AChE and 0.13 ± 0.01 μM for BChE), suggest a noteworthy anticholinergic capability. By providing detailed insights into the enzyme inhibition dynamics, this study lays the groundwork for optimizing nitrofuran derivatives in the therapeutic landscape of AD. The implications of these findings extend to the broader context of pharmacological advancements, highlighting the significance of targeted enzyme inhibition in managing neurodegenerative diseases. Future research building on these results could lead to the development of more effective treatments, enhancing the quality of life for individuals affected by AD and offering new avenues for clinical intervention.

Anahtar Kelimeler

• Acetylcholinesterase
• Butyrylcholinesterase
• Alzheimer
• Nitrofuran derivative
• Enzyme-ligand interactions

Kaynakça

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