Author/Editor		Bosak, Anita; Knežević, Anamarija; Gazić Smilović, Ivana; Šinko, Goran; Kovarik, Zrinka
Title		Resorcinol-, catechol- and saligenin-based bronchodilating [beta]2-agonists as inhibitors of human cholinesterase activity
Type		članek
Vol. and No.		Letnik 32, št. 1
Publication year		2017
Volume		str. 789-797
ISSN		1475-6366 - Journal of enzyme inhibition and medicinal chemistry
Language		eng
Abstract		We investigated the influence of bronchodilating [beta]2-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 Ki constants ranging from 9.4 [micro]M 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 [pi]-[pi] 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.
Keywords		acetylcholinesterase adrenaline butyrylcholinesterase acetilholinesteraza adrenalin butirilholinesteraza