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

Şalkonlar ilac gelistirme calismalarinda kullanisli, yenilikci ve biyoaktif kimyasal yapi iskeletleri olarak bilinirler. Bu calismada, bir dizi poli-metoksillenmis salkonlar (1-8) bazik kosul altinda Claisen-Schmidt kondansasyonu ile sentezlendi ve karbonik anhidraz (CA) I / II ve asetilkolinesteraz (AChE) inhibitor etkileri ilk olarak bu calismada degerlendirildi. 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 degerleri ile nanomolar konsantrasyonda inhibe edildi. Bilesikler, AChE enzimini 34.14 ± 20.79 - 53.65 ± 13.25 nM araliginda inhibe etti. Bilesik 1, 3 ve 5, sirasiyla hCA I, hCA II ve AChE'ye karsi en guclu inhibitorlerdir. Biyolojik aktivite sonuclari, bilesiklerin yeni salkon bazli enzim inhibitorleri tasarlamak icin ana yapi olarak kabul edilebildigini gosterdi. 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.