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Structure\u2013activity relationships (SARs) indicate that fluorine enhances BuChE selectivity through Tyr128 hydrogen bonding, hydrophobic extensions (\u03b1\u2010naphthyl substituted \u03b2\u2010carboline) optimise A\u03b2 disaggregation and C4\u20108 spacers (piperazine\u2010linked bivalent \u03b2\u2010carboline) facilitate dual\u2010target engagement without compromising blood\u2013brain barrier permeability. Validated pharmacophore models prioritise planar cores for \u03c0\u2013stacking, cationic centres for AChE\/NMDA targeting and flexible linkers, positioning these hybrids as clinically translatable, disease\u2010modifying candidates. In this extensive review, we summarised the derivatives and hybrids of carboline over the past decade for managing AD. We focus on their design, pharmacological activity and SAR analysis, as well as an exclusive pharmacophore model for both single\u2010 and multitarget carboline derivatives. We hope this review enhances the reader's understanding of future exploratory options for carboline hybrids in AD management.<\/jats:p>","DOI":"10.1002\/ardp.70166","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T04:34:49Z","timestamp":1766982889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Carboline Hybrids as Potential Multitarget\u2010Directed Anti\u2010Alzheimer's Disease Agents: A Comprehensive Analysis of Design Strategies and Structure\u2013Activity Relationships"],"prefix":"10.1002","volume":"358","author":[{"given":"Sandipan","family":"Dash","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University Institute of Pharma Sciences Chandigarh University Mohali Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-9143","authenticated-orcid":false,"given":"Arghya 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