engleski

Metaproterenol, isoproterenol and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors

Metaproterenol and isoproterenol are bronchodilators and form a structural basis of many other bronchodilators currently in use. Some bronchodilators need butyrylcholinesterase for bioconversion into active form. Bioconversion can be affected by a high level of BChE gene polymorphism as well as BChE stereoselectivity. Hence, we report our study on metaproterenol and isoproterenol as human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. We synthesized bisdimethylcarbamate derivatives of metaproterenol (metacarb) and isoproterenol (isocarb) to study the rates of their bioconversion by five human BChE variants. Homozygotes of usual, atypical and fluoride resistant BChE, heterozygote of usual and atypical as well as heterozygote of usual and fluoride resistant BChE were tested. Selectivity and stereoselectivity of AChE and four BChE variants towards enantiomers of bisdimethylcarbamates were determined experimentally and interpreted by molecular modeling.

butyrylcholinesterase variants; selectivity; stereoselectivity; prodrugs; bronchodilators

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