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The PI3K\/Akt signaling pathway and the aromatase enzyme are among the molecular targets that play a critical role in the development and progression of BC. In this study, novel benzothiazole\u2010triazole derivatives were synthesized, and their structures were confirmed using NMR and HRMS analyses. The cytotoxic activities of the eight synthesized compounds in the MCF\u20107\n                    <jats:sc>BC<\/jats:sc>\n                    cell line were evaluated using the MTT method, with NIH\/3T3 cells used as a healthy cell model. The IC\n                    <jats:sub>50<\/jats:sub>\n                    values of the compounds ranged from 10.186 to 52.020\u2009\u03bcM, with compounds\n                    <jats:bold>5b<\/jats:bold>\n                    ,\n                    <jats:bold>5f<\/jats:bold>\n                    , and\n                    <jats:bold>5h<\/jats:bold>\n                    showing the highest activity. Selectivity index results revealed that compound\n                    <jats:bold>5h<\/jats:bold>\n                    (SI\u2009=\u20095.986) exhibited the optimal selectivity profile along with strong anticancer activity. In enzyme inhibition studies, compound\n                    <jats:bold>5h<\/jats:bold>\n                    showed a strong inhibitory effect on Akt1, exhibiting activity close to the reference inhibitor with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 0.209\u2009\u00b1\u20090.011\u2009\u03bcM. However, the lack of significant inhibition of aromatase enzymes indicated that the compound displayed a more selective inhibitory profile towards Akt1. Mechanistic studies revealed that compound\n                    <jats:bold>5h<\/jats:bold>\n                    induced apoptotic cell death in MCF\u20107 cells, disrupted mitochondrial membrane potential, and caused high levels of caspase\u20103 activation. Furthermore, molecular docking and molecular dynamics simulations showed that the compound formed stable interactions in the Akt1 and PI3K active sites, supporting the experimental results. The findings indicate that compound\n                    <jats:bold>5h<\/jats:bold>\n                    is a promising anticancer candidate that targets the PI3K\/Akt signaling pathway.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70404","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:38:24Z","timestamp":1789706304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis, Structural Characterization, and Investigation of Biological Effects of Novel Benzothiazole\u2010Triazole Derivatives Designed as\n                    <scp>AKT<\/scp>\n                    Kinase Inhibitors"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-1209","authenticated-orcid":false,"given":"Bilge","family":"\u00c7ift\u00e7i","sequence":"first","affiliation":[{"name":"Institute of Graduate Education Anadolu University  Eski\u015fehir Turkey"},{"name":"Department of Medical Services Techniques Services, Vocational School of Health Services Bilecik Seyh Edebali University  Bilecik Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0368-0291","authenticated-orcid":false,"given":"Zeynep","family":"G\u00fclen\u00e7","sequence":"additional","affiliation":[{"name":"Institute of Graduate Education Anadolu University  Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0149-3065","authenticated-orcid":false,"given":"B\u00fc\u015fra","family":"Korkut \u00c7elikate\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Anadolu University  Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-436X","authenticated-orcid":false,"given":"Derya","family":"Osmaniye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Anadolu University  Eski\u015fehir Turkey"},{"name":"Central Research Laboratory, Faculty of Pharmacy Anadolu University  Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Abcam. n.d. 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