Naslov
Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases

Autori
Gazić, Ivana ; Bosak, Anita ; Šinko, Goran ; Vinković, Vladimir ; Kovarik, Zrinka

Izvornik
Analytical Bioanalytical Chemistry (1618-2642) 385 (2006), 8; 1513-1519

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cholinesterase; inhibition; bambuterol; enantiomers; preparative HPLC

Sažetak
We separated and characterized the enantiomers of bambuterol (5-[-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride), which is used in racemic form as a prodrug of terbutaline, a β 2-adrenoceptor agonist. The enantioseparation was tried on several chiral HPLC columns, and the most effective separation was achieved on amylose based Chiralpak AD column. Since in vivo conversion of bambuterol into terbutaline involves hydrolysis by butyrylcholinesterase (EC 3.1.1.8), we studied the reaction of enantiomers with eight human BChE variants. Both enantiomers inhibited all studied BChE variants, but the rate of inhibition with the (R)-enantiomer was about five times faster than with the (S)-enantiomer. (R)-bambuterol inhibition rate constants for homozygous usual (UU), fluoride-resistant (FF) or atypical (AA) variant ranged from 6.4 to 0.11 min-1 M-1. The inhibition rates for heterozygotes were between the respective constants for the corresponding homozygotes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA