Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity

Abstract

We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.

Levosalbutamol as alternative to drugs on the basis of racemic salbutamol: Review of the results of pre-clinical research

“…Исследователи заключили, что S-сальбутамол может перекрестно реагировать с мускариновыми рецепторами. При этом, Bosak et al (2017) в эксперименте с применением трех вариантов бутирилхолинэстеразы (BChE), выделенной из плазмы донорской крови, а также рекомбинантной АChE человека, установили, что β 2 -адреномиметики, в том числе сальбутамол, обладают свойствами обратимых ингибиторов холиэстеразы. При этом ингибиторная активность сальбутамола в отношении AChE (K i 2,0 ± 0,2 ммоль) почти в два раза превышает таковую у тербу-талина (4,8 ± 0,2 ммоль).…”

<p>Enhancing the Butyrylcholinesterase Activity in HEK-293 Cell Line by Dual-Promoter Vector Decorated on Lipofectamine</p>

“…4 Serum BChE is pharmacologically and toxicologically important, since the enzyme has the ability to hydrolyze ester drugs such as succinylcholine and cocaine and converts bambuterol into bronchodilating drug terbutaline. 5 BChE can be used either prophylactically or as a treatment drug. One of the most important applications of BChE is detoxifying organophosphate toxins.…”

Benzobicyclo[3.2.1]octene Derivatives as a New Class of Cholinesterase Inhibitors

“…Due to the composition of their active site, two enzymes can differ in selectivity and specificity for inhibitor binding [ 16 , 17 , 18 ]. Moreover, it has been well-documented that BChE reacts with a wider range of ligands than AChE and is less selective [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”