{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:26:12Z","timestamp":1788395172258,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi\u2013target\u2013directed ligands (MTDLs), we synthesized a series of (R)\u2013N\u2013(benzo[d]thiazol\u20132\u2013yl)\u20132\u2013(1\u2013phenyl\u20133,4\u2013dihydroisoquinolin\u20132(1H)\u2013yl) acetamides with substituted benzothiazoles and (S)\u20131\u2013phenyl\u20131,2,3,4\u2013tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO\u2013B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b\u20134d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO\u2013B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood\u2013brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.<\/jats:p>","DOI":"10.3390\/molecules27249062","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T09:05:09Z","timestamp":1671440709000},"page":"9062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, Characterization and Biological Evaluation of Benzothiazole\u2013Isoquinoline Derivative"],"prefix":"10.3390","volume":"27","author":[{"given":"Weihua","family":"Liu","sequence":"first","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Pharmacy College, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"He","sequence":"additional","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Hu","sequence":"additional","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhai","family":"Jin","sequence":"additional","affiliation":[{"name":"Pharmacy College, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-4506","authenticated-orcid":false,"given":"Liping","family":"Guan","sequence":"additional","affiliation":[{"name":"Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-3360","authenticated-orcid":false,"given":"Sihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Natural Resource of the Changbai Mountain and Functiaonal Molecules, Ministry of Education, Yanbian University, Yanji 133000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1242\/dmm.030205","article-title":"Neurodegenerative Disease: Models, Mechanisms, and a New Hope","volume":"10","author":"Gitler","year":"2017","journal-title":"DMM Dis. 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