Mehtap TUĞRAK, Cem YAMALI, Halise İnci GÜL, Yeliz DEMİR

Şalkonların karbonik anhidraz I, II ve asetilkolinesteraz enzimlerine karşı inhibisyon etkileri

Şalkonlar ilaç geliştirme çalışmalarında kullanışlı, yenilikçi ve biyoaktif kimyasal yapı iskeletleri olarak bilinirler. Bu çalışmada, bir dizi poli-metoksillenmiş şalkonlar (1-8) bazik koşul altında Claisen-Schmidt kondansasyonu ile sentezlendi ve karbonik anhidraz (CA) I / II ve asetilkolinesteraz (AChE) inhibitör etkileri ilk olarak bu çalışmada değerlendirildi. CA izoenzimleri olan I ve II, 8.75 ± 0.64 - 37.64 ± 2.38 nM (hCA I) ve 11.47 ± 3.31- 45.97 ± 4.67 nM (hCA II) Ki değerleri ile nanomolar konsantrasyonda inhibe edildi. Bileşikler, AChE enzimini 34.14 ± 20.79 - 53.65 ± 13.25 nM aralığında inhibe etti. Bileşik 1, 3 ve 5, sırasıyla hCA I, hCA II ve AChE'ye karşı en güçlü inhibitörlerdir. Biyolojik aktivite sonuçları, bileşiklerin yeni şalkon bazlı enzim inhibitörleri tasarlamak için ana yapı olarak kabul edilebildiğini gösterdi. Chalcones are known as versatile, innovative and bioactive chemical scaffolds in drug development studies. In this study, a series of poly-methoxylated chalcones (1-8) were synthesized by Claisen-Schmidt condensation under the basic condition and their carbonic anhydrase (CA) I/II and acetylcholinesterase (AChE) inhibitory effects were firstly evaluated in this study. CA isoenzymes I and II were inhibited in nanomolar concentration with Ki values of 8.75±0.64 - 37.64±2.38 nM (hCA I) and 11.47±3.31- 45.97±4.67 nM (hCA II). The compounds inhibited the AChE enzyme in the range of 34.14±20.79 - 53.65±13.25 nM. The compounds 1, 3 and 5 were the best inhibitors against hCA I, hCA II, and AChE, respectively. The bioassay results showed that the compounds can be considered as the main frame to design novel chalcone-based enzyme inhibitors.

Anahtar Kelimeler:

chalcone, carbonic anhydrase, acetylcholine esterase, enzyme inhibitor

Inhibitory effects of the chalcones towards carbonic anhydrase I, II and acetylcholinesterase enzymes

Chalcones are known as versatile, innovative and bioactive chemical scaffolds in drug development studies. In this study, a series of poly-methoxylated chalcones (1-8) were synthesized by Claisen-Schmidt condensation under the basic condition and their carbonic anhydrase (CA) I/II and acetylcholinesterase (AChE) inhibitory effects were firstly evaluated in this study. CA isoenzymes I and II were inhibited in nanomolar concentration with Ki values of 8.75±0.64 - 37.64±2.38 nM (hCA I) and 11.47±3.31- 45.97±4.67 nM (hCA II). The compounds inhibited the AChE enzyme in the range of 34.14±20.79 - 53.65±13.25 nM. The compounds 1, 3 and 5 were the best inhibitors against hCA I, hCA II, and AChE, respectively. The bioassay results showed that the compounds can be considered as the main frame to design novel chalcone-based enzyme inhibitors.

Keywords:

enzyme inhibitor, acetylcholinesterase, Chalcone,

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