{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T21:58:00Z","timestamp":1776203880266,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803367"],"award-info":[{"award-number":["81803367"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic Research and Frontier Exploration Project of Chongqing","award":["cstc2018jcyjAX0715"],"award-info":[{"award-number":["cstc2018jcyjAX0715"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["XDJK2019C103"],"award-info":[{"award-number":["XDJK2019C103"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer\u2019s disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values &lt; 10 \u03bcM on human BChE, selectivity index BChE &gt; 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.<\/jats:p>","DOI":"10.3390\/molecules24234217","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T11:06:03Z","timestamp":1574247963000},"page":"4217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations"],"prefix":"10.3390","volume":"24","author":[{"given":"You","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-8284","authenticated-orcid":false,"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiran","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life Science, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xifei","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingbin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Science, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-2886","authenticated-orcid":false,"given":"Qingyou","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. 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