Inhibicija kolinesterazâ karbamatom albuterola

master's thesis

• Title (english): Inhibition of cholinesterases by albuterol carbamate
• Author: Robert Kerep
• Mentor: Anita Bosak (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Committee member: Ivan Kodrin (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2018-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

OdreĎene su konstante brzine inhibicije dviju butirilkolinesteraza (BChE; EC 3.1.1.8) i dviju
acetilkolinesteraza (AChE; EC 3.1.1.7) s racemičnim, (R)- i (S)- N,N-dimetilkarbamatom
albuterola (4-(2-(tert-butilamino)-1-hidroksietil)-2-(hidroksimetil)fenol. Korištene su ljudska
(hBChE) i BChE izolirana iz seruma konja (hoBChE), rekombinantna ljudska AChE
(hAChE) i AChE izolirana iz električnog organa jegulje (eeAChE). Karbamat albuterola je
progresivno inhibirao sve ispitivane kolinesteraze s konstantama brzine inhibicije reda
veličine 103-106 dm3mol-1min-1, pri čemu je najbrţe inhibirao hBChE. Ispitivani karbamat se
pokazao selektivnim inhibitorom koji hBChE inhibira 8 puta brţe od hAChE. TakoĎer,
karbamat albuterola razlikuje kolinesteraze različitih vrsta, budući da hBChE inhibira 1,7 puta
brţe od hoBChE, dok hAChE inhibira 34 puta brţe od eeAChE. Ljudske BChE i AChE su
stereoselektivni enzimi koji imaju 13, odnosno 4 puta veći afinitet prema (R)-karbamatu
albuterola. Inhibicijski potencijal karbamata albuterola, kao i njegova selektivnost prema
hBChE u odnosu na AChE, manja je od do sada ispitivanih karbamata slične strukture.

Abstract (english)

Inhibition rate constants of two butyrylcholinesterases (BChE, EC 3.1.1.8) and two
acetylcholinesterases (AChE; EC 3.1.1.7) with racemic, (R)- and (S)- albuterol carbamate (4-
(2-(tert-butylamino )-1-hydroxyethyl)-2-(hydroxymethyl)phenyl dimethylcarbamate) were
determined. Human (hBChE) and BChE from the horse serum (hoBChE), recombinant
human AChE (hAChE) and AChE from the eel (eeAChE) were used. Albuterol carbamate
progressively inhibited all cholinesterases with inhibition rate constants ranged from 103-106
dm3mol-1min-1, wherefrom inhibition of hBChE was the fastest. Tested carbamate is a
selective BChE inhibitor inhibiting hBChE 8 times faster than hAChE. Also, albuterol
carbamate clearly distinguishes cholinesterases of different species, since it inhibits hBChE
1.7 times faster than hoBChE, and hAChE 34 times faster than eeAChE. Human BChE and
AChE are stereoselective enzymes having 13 or 4 times higher affinity to (R)-carbamate
albuterol. The inhibitory potential of albuterol carbamate, as well as its selectivity toward
hBChE relative to AChE, is lower than that of other carbamates with the similar structure.

• Keywords: acetilkolinesteraza; brzina karbamilacije; butirilkolinesteraza; selektivnost; stereoselektivnost
• Keywords (english): acetylcholinesterase; butyrylcholinesterase; carbamylation rate selectivity; stereoselectivity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:394151
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2019-02-26
• Created on: 2018-03-27 09:41:56