Metaproterenol, isoproterenol and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors

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

doi:10.1021/jm300289k

Pregled bibliografske jedinice broj: 550504

Metaproterenol, isoproterenol and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors

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

Metaproterenol, isoproterenol and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors // Journal of medicinal chemistry, 55 (2012), 15; 6716-6723 doi:10.1021/jm300289k (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 550504 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Metaproterenol, isoproterenol and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors

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

Izvornik
Journal of medicinal chemistry (0022-2623) 55 (2012), 15; 6716-6723

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

Ključne riječi
butyrylcholinesterase variants; selectivity; stereoselectivity; prodrugs; bronchodilators

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Javno zdravstvo i zdravstvena zaštita

POVEZANOST RADA

Projekti:
022-0222148-2889 - Interakcije organofosfata, karbamata i određenih liganada s esterazama (Kovarik, Zrinka, MZOS ) ( CroRIS)
098-0982904-2910 - Kiralni organski materijali – sintetska, strukturna i funkcionalna istraživanja (Vinković, Vladimir, MZOS ) ( CroRIS)

Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Institut "Ruđer Bošković", Zagreb

Profili:

Goran Šinko (autor)