XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
80.
STUDIES OF NOVEL BIvaLENT TACRINE DERIvaTIVES TarGETING
ACETYLCHOLINESTEraSES
Mária Kožurková 1 , Danica Sabolová 1 , Slávka Hamuľaková 1 , Jana Janočková 1 ,
Jana Plšíková 1 , Pavol Kristian 1 , Ján Imrich 1 , Ladislav Janovec 1 , Ondrej Holas 2 ,
Miroslav Pohanka 2 and Kamil Kuča 2
1
Institute of Chemistry, Faculty of Sciences, P.J. Šafárik University, Košice, SK
2
Faculty of Military Health Sciences, University of Defence, Hradec Králové, CZ
Derivatives of acridine/tacrine are effective drugs against Alzheimer disease (AD) which
is associated with the progressive memory loss and other cognitive impairments. The
primary approach to treating AD is delaying of symptoms of disease and increasing the
acetylcholinesterases levels in the brain by using acetylcholinesterase inhibitors. The
cholinesterase inhibitors have been identified according to their binding mode.
Eleven compounds of acridine/tacrine derivatives were synthesized and their properties
have been studied by UV-Vis, fluorescence spectrophotometry and circular dichroism.
The most promising inhibitor of acetylcholine from the newly prepared compounds were
derivative N-{2-[4-(acridine-9-yl) piperazino]etyl}-N-(1,2,3,4-tetrahydroacridine-9-yl)
amine (IC 50
= 0.003 ± 0.0006 µM) and N-(1,2,3,4-tetra-hydroacridine-9-yl)-N´-[2-(1,2,3,4-
tetrahydroacridine-9-ylamino)butyl]thiourea (IC 50
= 0.002 ± 0.0004 µM). These compounds
were two-fold stronger inhibitors compared to standards (tacrine and 7-MEOTA).
Acknowledgement: This work was supported by the Scientific Grant Agency VEGA
1/0053/08 and 1/0097/10 (Slovak Republic) and Ministry of Defence– OVUOFVZ200805
(Czech Republic).
XXII. Biochemistry Congress, Martin
203