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Enantiomers of Quinuclidin-3-ol Derivatives: Resolution and Interactions with Human Cholinesterases

Anita Bosak
Ines Primožić
Mislav Oršulić
Srdjanka Tomić
Vera Simeon-Rudolf


Puni tekst: engleski pdf 126 Kb

str. 121-128

preuzimanja: 803

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Sažetak

The (R)- and (S)-enantiomers of quinuclidin-3-ol and quinuclidin-3-yl acetate as well as their quaternary N-methyl and N-benzyl derivatives were synthesized in order to study the stereoselectivity of human erythrocyte acetylcholinesterase (EC 3.1.1.7) and plasma butyrylcholinesterase (EC 3.1.1.8). The compounds were tested as substrates and inhibitors of cholinesterases. Both cholinesterases hydrolyze the derivatives of quinuclidin-3-yl acetate with a preference for the (R)- over (S)-enantiomers. In contrast to the hydrolysis of the enantiomers of acetates, the inhibition of acetylcholinesterase and butyrylcholinesterase by the (R)- and (S)-enantiomers of quinuclidin-3-ol derivatives does not reveal enantiomeric preference of the enzymes. The (R)- and (S)-acetates also act as nonstereoselective inhibitors of the enzyme-induced hydrolysis of acetylthiocholine. The best substrate is (R)-N-methyl-3-acetoxyquinuclidinium iodide with kcat = 1.5 x 106 min–1 and kcat = 5.5 x 104 min–1 for acetylcholinesterase and butyrylcholinesterase, respectively. The (R)- and (S)-N-benzylquinuclidinium derivatives are the most potent inhibitors of both enzymes.

Ključne riječi

acetylcholinesterase, butyrylcholinesterase, chiral substrates and inhibitors, chiral quinuclidin-3-ol derivatives, chiral quinuclidin-3-yl acetates, stereoselectivity of cholinesterases

Hrčak ID:

2800

URI

https://hrcak.srce.hr/2800

Podaci na drugim jezicima: hrvatski

Posjeta: 1.542 *