{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:44:51Z","timestamp":1779918291090,"version":"3.53.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia","award":["14-MED-622-02"],"award-info":[{"award-number":["14-MED-622-02"]}]},{"name":"The National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia","award":["14-MED-622-02"],"award-info":[{"award-number":["14-MED-622-02"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Amyloid-\u03b21\u201342 (A\u03b242) peptide aggregate formation in the brain plays a crucial role in the onset and progression of Alzheimer\u2019s disease. According to published research, the A\u03b2 monomer\u2019s amino acid residues KLVFF (16\u201320) self-associate to create antiparallel \u03b2-sheet fibrils. Small compounds can prevent self-assembly and destroy A\u03b2 fibrils by attaching to the A\u03b216\u201320 regions of A\u03b242. To enhance biological characteristics and binding affinity to the amyloid beta peptide, \u03b2-sheet breaker small molecules can be developed and modified with various scaffolds. In the current study, a novel series of 2,3-disubstitutedbenzofuran derivatives was designed and created by fusing the benzofuran core of a known iron chelator, neuroprotective, and neurorestorative agent, like VK-28, with a motif found in the structure of a known muscarinic inhibitor and amyloid binding agent, like SKF-64346. Measurements of the binding affinity and in vitro aggregation inhibition of the A\u03b242 peptide were made using the thioflavin T (ThT) test. Using AutoDock 4.2 software, molecular docking studies of the synthesized compounds were performed on the monomer and fibril structures of amyloid beta peptide. The compounds <jats:bold>8a\u20138g<\/jats:bold> exhibited strong binding energy and affinity to A\u03b2 fibrils as well as a 50%\u201367% reduction of the growth of A\u03b2 aggregation. Finally, the positive traits of our recently synthesized compounds make them excellent candidates for additional <jats:italic>in vivo<\/jats:italic> testing as a \"\u03b2-sheet breaking agent.\"<\/jats:p>","DOI":"10.1371\/journal.pone.0286195","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T17:41:29Z","timestamp":1685036489000},"page":"e0286195","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Design and synthesis of multi-functional small-molecule based inhibitors of amyloid-\u03b2 aggregation: Molecular modeling and in vitro evaluation"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0269-7123","authenticated-orcid":true,"given":"Awwad A.","family":"Radwan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fars 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