Park, Byeongyeon Nam, Ji Hye Kim, Jin Han Kim, Hyoung Ja Onnis, Valentina Balboni, Gianfranco Lee, Kyung-Tae Park, Jeong Ho Catto, Marco Carotti, Angelo Lee, Jae Yeol 2024-01-20T02:01:51Z 2024-01-20T02:01:51Z 2021-09-01 2017-03-01 0960-894X https://pubs.kist.re.kr/handle/201004/122966 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. (C) 2017 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. STRUCTURE-BASED DESIGN ALZHEIMERS-DISEASE ACETYLCHOLINESTERASE INHIBITORS BIOLOGICAL EVALUATION POTENT ACHE DISCOVERY BUTYRYLCHOLINESTERASE BETA DEMENTIA LIGANDS 3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes Article 10.1016/j.bmcl.2017.01.068 1 Bioorganic & Medicinal Chemistry Letters, v.27, no.5, pp.1179 - 1185 Bioorganic & Medicinal Chemistry Letters 27 5 1179 1185 scie scopus 000395967900014 2-s2.0-85011884552 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article STRUCTURE-BASED DESIGN ALZHEIMERS-DISEASE ACETYLCHOLINESTERASE INHIBITORS BIOLOGICAL EVALUATION POTENT ACHE DISCOVERY BUTYRYLCHOLINESTERASE BETA DEMENTIA LIGANDS Alzheimer&apos s disease Cholinesterase inhibitors 3,4-dihydroquinazolines Molecular docking study Kinetic study