{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:25:27Z","timestamp":1764937527607,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mahidol University (Basic Research Fund","award":["BRF1-034\/2565"],"award-info":[{"award-number":["BRF1-034\/2565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>In this investigation, a number of phenoxyindole derivatives were designed, synthesized, and tested for their neuroprotective ability on SK-N-SH cells against A\u03b242-induced cell death and biologically specific activities involved in anti-A\u03b2 aggregation, anti-AChE, and antioxidant effects. The proposed compounds, except compounds 9 and 10, could protect SK-N-SH cells at the IC50 of anti-A\u03b2 aggregation with cell viability values ranging from 63.05% \u00b1 2.70% to 87.90% \u00b1 3.26%. Compounds 3, 5, and 8 demonstrated striking relationships between the %viability of SK-N-SH cells and IC50 values of anti-A\u03b2 aggregation and antioxidants. No significant potency of all synthesized compounds against AChE was found. Among them, compound 5 showed the strongest anti-A\u03b2 and antioxidant properties with IC50 values of 3.18 \u00b1 0.87 and 28.18 \u00b1 1.40 \u03bcM, respectively. The docking data on the monomeric A\u03b2 peptide of compound 5 demonstrated good binding at regions involved in the aggregation process, and the structural feature made it possible to be a superior radical scavenger. The most effective neuroprotectant belonged to compound 8, with a cell viability value of 87.90% \u00b1 3.26%. Its unique mechanisms for enhancing the protective impact may serve additional purposes since it demonstrated mild biological-specific effects. In silico prediction of CNS penetration shows strong passive penetration ability across the blood\u2013brain barrier from blood vessels to the CNS for compound 8. In light of our findings, compounds 5 and 8 appeared as potentially intriguing lead compounds for new therapeutic approaches to Alzheimer\u2019s disease. More in vivo testing will be revealed in due course.<\/jats:p>","DOI":"10.3390\/ph16030355","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:15:37Z","timestamp":1677464137000},"page":"355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Design, Synthesis, and Neuroprotective Activity of Phenoxyindole Derivatives on Antiamyloid Beta (A\u03b2) Aggregation, Antiacetylcholinesterase, and Antioxidant Activities"],"prefix":"10.3390","volume":"16","author":[{"given":"Somjate","family":"Laivut","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Primchanien","family":"Moongkarndi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Worawan","family":"Kitphati","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-4226","authenticated-orcid":false,"given":"Pattarawit","family":"Rukthong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Nakornnayok 26120, Thailand"},{"name":"Center for Excellence in Plant and Herbal Innovation Research, Strategic Wisdom and Research Institute, Srinakharinwirot University, Nakornnayok 26120, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1276-9266","authenticated-orcid":false,"given":"Korbtham","family":"Sathirakul","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-4684","authenticated-orcid":false,"given":"Kittisak","family":"Sripha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"},{"name":"Unit of Compounds Library for Drug Discovery Mahidol University, 447 Sri-Ayudhya Rd., Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/nbdi.1997.0147","article-title":"Biology of A\u03b2 amyloid in Alzheimer\u2019s disease","volume":"4","author":"Wisniewski","year":"1997","journal-title":"Neurobiol. 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