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Alepterolic acid, a labdane\u2010type diterpenoid firstly isolated from <jats:italic>Aleuritopteris argentea<\/jats:italic> (Gm\u00e9l.) F\u00e9e, has been identified as a valuable template for the synthesis of potent anticancer agents by structural modification. In this study, a series of new derivatives was obtained by coupling alepterolic acid with benzylpiperazines. It was found that (3,4\u2010dichlorobenzyl)piperazinyl alepterolic acid (compound <jats:bold>6p<\/jats:bold>) displayed the highest level of toxicity against MCF\u20107\u2005cell line, with an IC<jats:sub>50<\/jats:sub> value of 8.31\u00b10.67\u2005\u03bcM. Further investigations demonstrated that compound <jats:bold>6p<\/jats:bold> induced morphological changes in MCF\u20107 cells, inhibited proliferation in a time\u2010 and dose\u2010dependent manner. Furthermore, western blot analysis revealed that compound <jats:bold>6p<\/jats:bold> induced a significant increase in cleaved caspase\u20109, cleaved caspase\u20103, cleaved poly (ADP\u2010ribose) polymerase (PARP) and Bax\/Bcl\u20102 ratio in MCF\u20107 cells. All of these results confirmed that compound <jats:bold>6p<\/jats:bold> induced endogenous apoptosis in MCF\u20107 cells. Conclusively, the findings suggest that the incorporation of benzylpiperazine to alepterolic acid represents a promising approach for the discovery of new drug candidates.<\/jats:p>","DOI":"10.1002\/cbdv.202401706","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T12:24:00Z","timestamp":1729686240000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Benzylpiperazinyl Derivatives of Alepterolic Acid: Synthesis and Cytotoxic Evaluation"],"prefix":"10.1002","volume":"22","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"College of Life Sciences Shanghai Normal University  Shanghai 201418 P.R. 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