Preparation, in Vitro Screening and Molecular Modelling of Symmetrical Bis-Quinolinium Cholinesterase Inhibitors--Implications for Early Myasthenia Gravis Treatment

Marketa Komloova, Kamil Musilek, Anna Horova, Ondrej Holas, Vlastimil Dohnal, Frank Gunn-Moore, Kamil Kuca

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2505-9.

PMID: 21397501

Abstract:

This paper describes the preparation and in vitro evaluation of 18 newly prepared bis-quinolinium inhibitors on human recombinant acetylcholinesterase (AChE) and human plasmatic butyrylcholinesterase (BChE). Their inhibitory (IC(50)) and was compared to the chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. One novel compound was found to be a promising inhibitor of hAChE (in nM range) and was better than edrophonium chloride or BW284c51, but was worse than ambenonium chloride. This compound also showed selectivity towards hAChE and it was confirmed as a non-competitive inhibitor of hAChE by kinetic analysis. A molecular modelling study further confirmed its binding to the peripheral active site of hAChE via apparent π-π or π-cationic interactions.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1094082	Ethopropazine hydrochloride		1094-08-2	Price