{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T18:27:41Z","timestamp":1786386461492,"version":"build-2736575974"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["SC3GM140980"],"award-info":[{"award-number":["SC3GM140980"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Multi-mechanistic sigma-1 (\u03c31) receptors are implicated in several neurodegenerative pathologies including Alzheimer's disease (AD). As part of an ongoing effort to create a collection of diverse, readily synthesizable, \u03c31 acting small molecules for anti-neurodegenerative applications, we opted to try lipoic acid (LA) derived amides. These amides are designated as \u201c5-(1,2 dithiolan-3-yl)pentanamides\u201d throughout this publication. Our design approach was \u03c31 pharmacophore based \u2013 that is, ligands possessing three key functionalities (a hydrophobic dithiolane group, a flexible amide H-bonding linker, a hydrophobic alkyl\/aryl group). Twenty-one dithiolane pentanamides were therefore designed, docked, synthesized, and pharmacologically assessed for \u03c31\/\u03c32 binding affinities. Compounds\n                    <jats:bold>2, 6, 17<\/jats:bold>\n                    possessed promising selective \u03c31 binding affinities (with respective Ki values of 256, 133 and 32 nM) versus the standard ligand\n                    <jats:bold>PD144418<\/jats:bold>\n                    (Ki\u2009=\u20090.08 nM). The three compounds will be used as leads in follow-up structure activity optimizations.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352906","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T17:28:07Z","timestamp":1786382887000},"page":"e0352906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bis-hydrophobic 5-(1,2-dithiolan-3-yl)pentanamide budding leads targeting brain sigma-1 receptors"],"prefix":"10.1371","volume":"21","author":[{"given":"Rafael","family":"Flores","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapembwa","family":"Musenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyse Brito","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan 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