Synthesis of new piperazine compounds and investigation of their anticholinesterase effects

Abstract

Purpose: The aim of present study is to evaluate anticholinesterase activities of some new piperazine compounds.

Materials and Methods: Ten new piperazine derivatives were synthesized. Structure elucidation of the synthesized compounds was performed by spectroscopic medhods.  Inhibitory activities of these compounds on acetylcholine esterase (AChE) and butrylcholine esterase (BChE) enzymes have been determined by Ellman’s colorimetric assay. Enzyme kinetic studies were performed for the most active compound 2b by using Lineweaver–Burk plots.

Results: The compound 2b including chloro substituent was found as the most active derivative with 82.95 %, 66.93 % and 42.63 % inhibition rates at 1 mM, 0.1 mM and 0.01 mM concentrations, respectively. Non-competitive type of inhibition was determined for compound 2b as a result of enzyme kinetic studies. 

Conclusion: None of the compounds showed activity as much as standard drug donepezil. However, compound 2b and 2c displayed a promising and selective inhibitory activity against AChE.

Keywords

• AChE,BChE,Piperazine,inhibition

Yeni piperazin bileşiklerinin sentezi ve antikolinesteraz etkilerinin araştırılması

Öz

Amaç: Bu çalışmada bazı yeni piperazin bileşiklerinin antikolinesteraz etkinliklerinin değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: On yeni piperazin türevi sentezlenmiştir. Sentezlenen bileşiklerin yapı aydınlatmaları spektroskopik yöntemler ile gerçekleştirilmiştir. Bu bileşiklerin asetilkolin esteraz (AChE) ve butirilkolin esteraz enzimleri üzerindeki etkileri, Elmann kolorimetrik metodu ile belirlenmiştir. En etkili 2b bileşiği için Lineweaver–Burk grafiği kullanılarak enzim kinetik çalışmaları gerçekleştirilmiştir.

Bulgular: Klor değişken grubu içeren 2b kodlu bileşiğin 1mM, 0.1 mM and 0.01 mM konsantrasyonlarda sırasıyla % 82.95, % 66.93 ve %42.63 inhibisyon oranları ile en etkili türev olduğu belirlenmiştir. Enzim kinetik çalışmaları sonucunda 2b kodlu bileşiğin non-kompetitif tip inhibisyon gösterdiği tespit edilmiştir.

Sonuç: Hiçbir bileşik standart ilaçlar donepezil ve takrin kadar etki göstermemiştir. Ancak 2b ve 2c kodlu bileşikler AChE enzimine karşı seçici ve umut verici düzeyde inhibisyon sergilemiştir.

Anahtar Kelimeler

• AChE,BChE,Piperazin,inhibisyon.

Kaynakça

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