REPUBLIC OF SERBIA

MINISTRY OF DEFENCE

www.mod.gov.rs

MINISTRY OF DEFENCE

Material Resources Sector

Defensive Technologies Department

Military Technical Institute

www.vti.mod.gov.rs

Anticholinesterase activity of 4-aryl-4-oxo-N-phenyl-2-aminylbutyramides

tamarA B. vujatović

Faculty of Chemistry, University of Belgrade, tamara.vujatovic@gmail.com

MAJA D. VITOROVIĆ-TODOROVIĆ

Military Technical Institute, Belgrade, mvitod@chem.bg.ac.rs

SONJA Đ. BAUK

Military Technical Institute, Belgrade, bauk.sonja@gmail.com

Abstract: Acetylcholinesterase (EC 3.1.1.7) is an enzyme which terminates cholinergic neurotransmission, by hydrolyzing acetylcholine at nerve and nerve-muscle junctions. Organophosphorous chemical warfare agents (i.e. nerve agents) exhibit their toxic effects mainly through covalent irreversible inhibition of acetylcholinesterase. The reversible inhibition of AChE was suggested as the pretreatment option of nerve agents’ intoxications. In the present work we synthesized series of Michael adducts of the three amines1-benzyl-4-piperidinamine, 4-benzylpiperidine and N,N-dimethyl-N-[2-(1-piperazinyl)ethyl]amine on aroylacrylic acid phenylamides. Fifteen derivatives were synthesized with variation of substituents on aroyl- and phenylamide rings. The compounds were characterized by 1H and 13C NMR spectroscopy. The inhibitory activity toward acetylcholinesterase was tested using Ellman assay. Several compounds showed low micromolar activity toward acetylcholinesterase.

Keywords: Acetylcholinesterase, nerve agents, pretreatment, aroylacrylic acid derivatives, reversible inhibition