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This study evaluated the antiproliferative activity of compound\n                    <jats:bold>1<\/jats:bold>\n                    and thirty\u2010three\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>9<\/jats:sup>\n                    \u2010substituted derivatives across a panel of cancer cell lines representing various histotypes. Among these, derivative\n                    <jats:bold>6<\/jats:bold>\n                    , a harmine analog bearing a 3,5\u2010dimethylbenzyl substituent, was the most potent, showing enhanced cytotoxicity and selectivity toward cancer cells. Compound\n                    <jats:bold>6<\/jats:bold>\n                    exhibited IC\n                    <jats:sub>50<\/jats:sub>\n                    values below 10\u2009\u00b5M in all tested cancer cell lines, while its IC\n                    <jats:sub>50<\/jats:sub>\n                    in non\u2010cancerous cells exceeded 100\u2009\u00b5M. Viability assays and xCELLigence real\u2010time monitoring confirmed a concentration\u2010dependent inhibition of cancer cell growth with minimal effects on non\u2010malignant cells. Flow cytometry demonstrated G1 phase arrest in MOLT\u20104 cells, supported by Western blot data showing reduced phosphorylated Rb and increased p27 protein levels. Apoptosis induction was confirmed through Annexin V\/PI staining, TUNEL assays, and caspase activation studies. These revealed the involvement of both intrinsic (caspase\u20109) and extrinsic (caspase\u20108) apoptotic pathways, along with activation of caspases 3\/7. Western blot analysis also showed a concentration\u2010dependent increase in the Bax\/Bcl\u20102 ratio. Immunofluorescence microscopy visualization indicated DNA damage through elevated levels of PAR and \u03b3H2AX, consistent with single\u2010 and double\u2010strand DNA breaks. Importantly, compound\n                    <jats:bold>6<\/jats:bold>\n                    exhibited low inhibitory activity against monoamine oxidase A (MAO\u2010A) and did not promote reactive oxygen species (ROS) generation, minimizing potential off\u2010target effects. Together, these findings support the potential of compound\n                    <jats:bold>6<\/jats:bold>\n                    as a selective and effective candidate for antileukemia therapy.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70197","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:16:07Z","timestamp":1770794167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harmine Derivatives as Anticancer Agents Endowed With Potent and Selective Antileukemia Activity: Synthesis, Biological Evaluation, Proapoptotic and Genotoxic Activity"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5960-0374","authenticated-orcid":false,"given":"Abdul Aziz","family":"Timbilla","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine in Hradec Kralove Charles University  Hradec Kralove Czech 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