Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions

Abstract

A series of diaryl ethers were synthesized and their human (h) carbonic anhydrase (CA) isoenzymes hCA I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitory actions were investigated. The new compounds were synthesized from the corresponding phenols and bromobenzenes via the Ullmann reaction, by using dipicolinic acid as a copper (I) complexing ligand. hCA I and II were inhibited with K_is in the low nanomolar range of 102.01–127.13 nM against hCA I, and of 73.71–113.40 nM against hCA II, whereas the inhibition constants against AChE were of 15.35–18.34 nM and against BChE in the range of 9.07–22.90 nM. The CA inhibition mechanism with these ethers is unknown, but may be similar to that of aryl methyl ethers investigated earlier by computational approaches.

Keywords:

• Acetylcholinesterase
• butyrylcholinesterase
• carbonic anhydrase
• diaryl ethers
• enzyme inhibition

Declaration of interest

There is no declaration of interest for this work. The authors are indebted to the Scientific and Technological Research Council of Turkey (TÜBİTAK, Grant No. 115Z422) for financial support of this work.