Synthesis,biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases |
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| Institution: | 1. Department of Chemistry, University of Sargodha, Sargodha, Pakistan;2. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;3. School of Science & Engineering, Teesside University, Tees Valley, Middlesbrough TS1 3BA, UK;4. Department of Pharmacy, University of Malakand, Chakdara 18000, Dir (L), Pakistan;1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor, Malaysia;2. Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia;3. Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan;4. Batterje Medical College for Science & Technology, Jeddah 21442, Saudi Arabia;5. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;1. Department of Applied Chemistry, Faculty of Science, Shiraz Branch, Islamic Azad University, P.O. Box 71993-5 Sadra new city, Shiraz, Iran;2. Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran;3. Department of Industrial Polymer Engineering, Shiraz Branch, Islamic Azad University, Sadra new city, Shiraz, Iran;1. Jiangxi 2011 Joint Center for the Innovative Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang 330013, China;2. School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013, China;1. Department of Chemistry, School of Advanced Sciences, VIT, Vellore-632014, Tamil Nadu, India;2. Organic and Bio-Organic Chemistry Division, Council of Scientific and Industrial Research (CSIR)-Central Leather Research Institute (CLRI), Adyar, Chennai 600020, India;1. Student Research Committee, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;3. Department of Chemistry, Shiraz University, Shiraz, Iran;4. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran |
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| Abstract: | In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC50 = 1.6 ± 0.10 μM (AChE) and 3.7 ± 0.18 μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme. |
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| Keywords: | 2 3-Dihydroquinazolin-4(1H)-one Dual inhibitors Cholinesterases Alzheimer’s disease |
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