Naslov
Interactions of enantiomers of quinuclidin-3-ol derivatives with human cholinesterases

Autori
Simeon-Rudolf, Vera ; Bosak, Anita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
VIII International Meeting on Cholinesterases: Program and Abstracts / Talesa, Vincenzo N. ; Antognelli Cinzia - Perugia : Universita degli Studi di Perugia, 2004

Skup
VIII International Meeting on Cholinesterases

Mjesto i datum
Perugia, Italija, 26.09.2004. - 30.09.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
enantiomeri; derivati kinuklidin-3-ola; humane kolinesteraze
(enantiomers; quinuclidin-3-ol derivatives; human cholinesterases)

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 studied with respect to 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 of acetycholinesterase and butyrylcholinesterase, and/or as inhibitors of the enzymes. The hydrolysis of the esters catalysed by the enzymes was followed by pH-stat titration of the liberated acetic acid. Stereoselectivity of the cholinesterases was observed in the hydrolysis of all derivatives of quinuclidin-3-yl acetate with a preference for the (R)- over (S)-enantiomers. The best substrate for both enzymes was (R)-N-methyl acetate with kcat = 2.8 x 105 min-1 and kcat = 3.0 x 104 min-1 for acetylcholinesterase and butyrylcholinesterase, respectively. However, the (S)-quinuclidine acetates interacted with the cholinesterases as competitive inhibitors. The inhibition of the enzymes by the (S)-quinuclidine acetates and (R)- and (S)-enantiomers of quinuclidin-3-ol derivatives was measured spectrophotometrically with acetylthiocholine as substrate. The cholinesterases were reversibly inhibited by both enantiomers of quinuclidin-3-ol derivatives but without explicit enantiomeric preference. Competition with acetylthiocholine revealed binding of the inhibitors to the catalytic and/or peripheral site of the enzymes. The enantiomers of N-benzylquinucldinium-3-ol were better inhibitors than the other alcohols and the dissociation constants of the enzyme-inhibitor complexes were between 0.042 and 0.74 mol L-1.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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