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Purine derivatives are recognised for their anticancer potential, making them valuable candidates for drug development. In the present study, we sought to uncover the anticancer potential of novel 6\u2010cycloalkylaminoadenine compounds and elucidate their mechanism of action. A versatile synthetic pathway was developed to prepare two series of new 6\u2010cycloalkylaminoadenines that combine the adenine scaffold with morpholino and\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methylpiperazine units. The method starts with the preparation of imidazole\u2010based amidrazone precursors, which were obtained from 5\u2010amino\u20104\u2010cyanoformimidoylimidazoles and 4\u2010aminomorpholine or 4\u2010methylaminopiperazine. The reaction of these amidrazone precursors with triethyl orthoformate under reflux gave the target 6\u2010cycloalkylaminoadenines. The compounds' cytotoxicity on the TNBC cell line MDA\u2010MB\u2010231 was assessed, with the best IC\n                    <jats:sub>50<\/jats:sub>\n                    values around 60\u201370\u2009\u03bcM. The most promising compound,\n                    <jats:bold>3.2a<\/jats:bold>\n                    , inhibits the migratory and invasive capacities of TNBC cells and promotes actin cytoskeleton reorganisation. Additionally, this compound induces caspase\u20103 activation, which promotes DNA fragmentation and ultimately leads to cell death. Molecular docking studies with key proteins involved in major signalling pathways associated with cancer progression further revealed that compound\n                    <jats:bold>3.2a<\/jats:bold>\n                    has a higher affinity for CDK1. Altogether, our findings provide preliminary evidence supporting the potential of 6\u2010cycloalkylaminoadenines in TNBC treatment.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70336","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:11:20Z","timestamp":1780639880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <scp>\n                      <i>N<\/i>\n                      <sup>9<\/sup>\n                    <\/scp>\n                    \u2010Substituted 6\u2010Cycloalkylaminoadenines as Promising Compounds Against Triple Negative Breast Cancer"],"prefix":"10.1111","volume":"107","author":[{"given":"Ana Catarina","family":"Pereira","sequence":"first","affiliation":[{"name":"CEB\u2010Centre of Biological Engineering University of Minho  Braga Portugal"},{"name":"CQUM\u2010Centre of Chemistry University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraia P.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CQUM\u2010Centre of Chemistry University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Leite","sequence":"additional","affiliation":[{"name":"CQUM\u2010Centre of Chemistry University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Vieira","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE BioSIM\u2013Department of Biomedicine, Faculty of Medicine University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1tia","family":"Santos\u2010Pereira","sequence":"additional","affiliation":[{"name":"CEB\u2010Centre of Biological Engineering University of Minho  Braga Portugal"},{"name":"LABBELS\u2013Associate Laboratory  Braga Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Ferreira","sequence":"additional","affiliation":[{"name":"CEB\u2010Centre of Biological Engineering University of Minho  Braga Portugal"},{"name":"LABBELS\u2013Associate Laboratory  Braga Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio F.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Faculty of Sciences and Technology University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5111-0774","authenticated-orcid":false,"given":"Alice","family":"Dias","sequence":"additional","affiliation":[{"name":"CQUM\u2010Centre of Chemistry University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-0630","authenticated-orcid":false,"given":"L\u00edgia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CEB\u2010Centre of Biological Engineering University of Minho  Braga Portugal"},{"name":"LABBELS\u2013Associate Laboratory  Braga Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2007.05994.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13446"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14122694"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c02991"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302\u20100388pp"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097\u20102765(03)00392\u20107"},{"key":"e_1_2_11_9_1","first-page":"1979","volume-title":"Head and Neck","author":"Behbahani T. 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