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 Kis 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.
MeSH terms
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Acetylcholinesterase / metabolism*
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Butyrylcholinesterase / metabolism*
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Carbonic Anhydrase I / antagonists & inhibitors
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Carbonic Anhydrase I / isolation & purification
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Carbonic Anhydrase I / metabolism
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Carbonic Anhydrase II / antagonists & inhibitors
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Carbonic Anhydrase II / isolation & purification
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Carbonic Anhydrase II / metabolism
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry
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Carbonic Anhydrase Inhibitors / pharmacology*
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Cholinesterase Inhibitors / chemical synthesis
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Ethers / chemical synthesis*
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Ethers / chemistry
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Ethers / pharmacology*
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / isolation & purification
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Isoenzymes / metabolism
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Molecular Structure
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Structure-Activity Relationship
Substances
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Carbonic Anhydrase Inhibitors
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Cholinesterase Inhibitors
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Ethers
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Isoenzymes
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Acetylcholinesterase
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Butyrylcholinesterase
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Carbonic Anhydrase I
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Carbonic Anhydrase II