title: 3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes.
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 IC50values of 45nM and 62nM, 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.
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Byeongyeon
authors.initials: B
authors.lastname: Park
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Nam
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Jin Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Molecular Recognition Research Center, Future Convergence Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Hyoung Ja
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Via Ospedale 72, I-09124 Cagliari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Onnis
authors.affiliation: Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Via Ospedale 72, I-09124 Cagliari, Italy. Electronic address: gbalboni@unica.it.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Department of Chemical & Biological Engineering, Hanbat National University, Daejeon 34158, Republic of Korea.
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Catto
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", via E. Orabona, 4, I-70125 Bari, Italy. Electronic address: angelo.carotti@uniba.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
authors.affiliation: Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: ljy@khu.ac.kr.
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D011799:Quinazolines
keywords: 3,4-dihydroquinazolines; Alzheimer’s disease; Cholinesterase inhibitors; Kinetic study; Molecular docking study