3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes

Title
3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes
Authors
김형자Byeongyeon ParkJi Hye NamJin Han NamValentina OnnisGianfranco BalboniKyung-Tae LeeJeong Ho ParkMarco CattoCarotti, AngeloLee, Jae Yeol
Keywords
Alzheimer’s disease; Cholinesterase inhibitors; 3,4-dihydroquinazolines; Molecular docking study; Kinetic study
Issue Date
2017-03
Publisher
Bioorganic & medicinal chemistry letters
Citation
VOL 27, NO 5-1185
Abstract
A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and strong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC50 values of 45 nM and 62 nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of 3,4-dihydroquinazoline derivatives. As expected, compound 8b and 8d bind to both catalytic anionic site (CAS) and peripheral site (PS) of BChE with better interaction energy values than AChE, in agreement with our experimental data. Furthermore, the non-competitive/mixed-type inhibitions of both compounds further confirmed their dual binding nature in kinetic studies.
URI
http://pubs.kist.re.kr/handle/201004/66424
ISSN
0960-894X
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KIST Publication > Article
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