Mehtap TUĞRAK, Halise İnci GÜL, Barış ANIL, Hülya AKINCIOĞLU

Design, Synthesis and Biological Activities of Chalcones with Piperonal Moiety

Heterosiklik bileşikler, farmakolojik olarak aktif bileşikler arasında özel bir öneme sahiptir. Bu çalışmada, bazı piperonal bazlı şalkonlar (PC1-PC10), 3,4-metilendioksibenzaldehid ve birkaç asetofenon arasında Claisen-Schmidt Kondenzasyonu ile sentezlendi. Bileşiklerin inhibitör etkileri, insan karbonik anhidraz I, II enzimlerine (hCA I ve hCA II) ve asetilkolinesteraz (AChE) enzimine karşı araştırıldı. Şalkon türevlerinin, hCA I için 5.11-109.70 μM, hCA II için 17.05-162.59 μM ve AChE için 18.52-98.69 μM aralığında IC50 değerlerine sahip olduğu görüldü. Tüm bileşikler referans bileşiklerden daha düşük inhibisyon potansiyeli gösterdi. Fakat PC3 (metoksi) hCA I ve hCA II karşı, PC5 (flor) AChE'ye karşı söz konusu yeni daha güçlü bileşikler geliştirmek için serinin aday bileşikleri olarak belirlendi.

Anahtar Kelimeler:

Alzheimer disease, chalcone, carbonic anhydrase, piperonal, acetylcholinesterase

Piperonal Artığı Taşıyan Şalkonların Dizaynı, Sentezi ve Biyolojik Aktiviteleri

Heterosiklik bileşikler, farmakolojik olarak aktif bileşikler arasında özel bir öneme sahiptir. Bu çalışmada, bazı piperonal bazlı şalkonlar (PC1-PC10), 3,4-metilendioksibenzaldehid ve birkaç asetofenon arasında Claisen-Schmidt Kondenzasyonu ile sentezlendi. Şalkonların inhibisyon potansiyelleri insan karbonik anhidraz I, II enzimlerine (hCA I ve hCA II) ve asetilkolinesteraz (AChE) enzimine karşı araştırıldı. Şalkon türevlerinin, hCA I için 5.11-109.70 μM, hCA II için 17.05-162.59 μM ve AChE için 18.52-98.69 μM aralığında IC50 değerlerine sahip olduğu görüldü. Tüm bileşikler referans bileşiklerden daha düşük inhibisyon potansiyeli gösterdi. PC3 (metoksi türevi) bileşiği hem hCA I hemde hCA II’ye karşı en etkili bileşik olurken, PC5 (flor türevi) AChE'ye karşı seri içinde en güçlü inhibitör etki göstermiştir. Sonuçlar, şalkon türevleri PC3 ve PC5'in hCA I, hCA II ve AChE izoenzimlerine karşı daha güçlü enzim inhibitörleri tasarlamada uygun adaylar olarak kabul edilebileceğini doğrulamıştır.

Keywords:

Alzheimer Hastalığı, karbonik anhidraz, , şalkon,

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