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The objective of the current research is to evaluate different NSAIDs using computer\u2010aided drug design (CADD) to explore their potential as new treatments for AD. CADD is an advanced technique for designing biologically active molecules and involves two primary approaches: structure\u2010based virtual screening and ligand\u2010based virtual screening. After identifying the NSAID with the highest affinity for amyloid A\u03b21\u201342 fibrils (PDB 2BEG), we designed analogs through bioisosteric modifications. Twenty derivatives were created, and two carprofen analogs with the most promising properties were synthesized, yielding 75% success with compound A\u20101 and 70% with compound A\u20102. These analogs exhibited lower predicted IC\n                    <jats:sub>50<\/jats:sub>\n                    values (1.57\u2009\u03bcM) and more negative interaction energies (\u22126.43 and \u22126.67\u2009kcal\/mol for A\u20101 and A\u20102, respectively) compared to carprofen. Safety evaluations in L929 cells indicated that these compounds were safe at concentrations of 40\u2009\u00b5M. In conclusion, two carprofen analogs were successfully designed and synthesized, demonstrating higher affinity for the amyloid A\u03b21\u201042 fibrils, better\u2010predicted IC\n                    <jats:sub>50<\/jats:sub>\n                    values than carprofen, and safety in the L929\u2009in vitro assay.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70393","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:47:35Z","timestamp":1784166455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computer\u2010Aided Drug Design, Synthesis, and In Vitro Safety Evaluation of Carprofen Analogs for Novel Alzheimer\u2019s Disease Therapeutics"],"prefix":"10.1002","volume":"21","author":[{"given":"Paola","family":"Acosta\u2010Guzm\u00e1n","sequence":"first","affiliation":[{"name":"Investigaci\u00f3n en Qu\u00edmica Aplicada INQA Qu\u00edmica Farmac\u00e9utica Universidad el Bosque  Bogot\u00e1 Colombia"},{"name":"Departamento de Qu\u00edmica Facultad de Ciencias Universidad Nacional de Colombia  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bedoya\u2010Malag\u00f3n","sequence":"additional","affiliation":[{"name":"Investigaci\u00f3n en Qu\u00edmica Aplicada INQA Qu\u00edmica Farmac\u00e9utica Universidad el Bosque  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Mercado\u2010Coy","sequence":"additional","affiliation":[{"name":"Investigaci\u00f3n en Qu\u00edmica Aplicada INQA Qu\u00edmica Farmac\u00e9utica Universidad el Bosque  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Johanna","family":"Morantes","sequence":"additional","affiliation":[{"name":"Investigaci\u00f3n en Qu\u00edmica Aplicada INQA Qu\u00edmica Farmac\u00e9utica Universidad el Bosque  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-3719","authenticated-orcid":false,"given":"James","family":"Guevara\u2010Pulido","sequence":"additional","affiliation":[{"name":"Investigaci\u00f3n en Qu\u00edmica Aplicada INQA Qu\u00edmica Farmac\u00e9utica Universidad el Bosque  Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414686200"},{"key":"e_1_2_9_3_1","unstructured":"ALZHEIMER'S ASSOCIATION REPORT Alzheimers Dement 19(2023):1598\u20131695."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2224887"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2220032"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2214224"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2232024"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.127553"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010094"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02324-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00299-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000078501"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158185"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36167-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130275"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160612"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.57078"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0610200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.04.070"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2018.09.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2023.101888"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa109"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.82.85"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.29090\/psa.2024.01.23.1061"},{"key":"e_1_2_9_25_1","first-page":"19","article-title":"Are NSAIDs Useful to Treat Alzheimer's Disease or Mild Cognitive Impairment?","volume":"2","author":"Imbimbo B. 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