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(i)s in the low nanomolar range of 102.01-127.13nM against hCA I, and of 73.71-113.40nM against hCA II, whereas the inhibition constants against AChE were of 15.35-18.34nM and against BChE in the range of 9.07-22.90nM. The CA inhibition mechanism with these ethers is unknown, but may be similar to that of aryl methyl ethers investigated earlier by computational approaches.