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In this study, alepterolic acid was modified to construct a series of arylformyl piperazinyl derivatives (<jats:bold>3a<\/jats:bold>\u2013<jats:bold>3p<\/jats:bold>). The synthesized derivatives were fully characterized with HRMS, NMR, and IR. Four compounds with inhibition rate higher than 30\u2009% at 10\u2005\u03bcM (<jats:bold>3f<\/jats:bold>, <jats:bold>3n<\/jats:bold>, <jats:bold>3g<\/jats:bold> and <jats:bold>3k<\/jats:bold>) were further measured to obtain the IC<jats:sub>50<\/jats:sub> values against four cancer cell lines, including hepatoma cell lines HepG2, lung cancer cell lines A549, estrogen receptor\u2010positive cell lines MCF7, and triple\u2010negative breast cancer (TNBC) cell lines MDA\u2010MB\u2010231 by MTT assay. It was found that these compounds were more effective to HepG2 and MDA\u2010MB\u2010231 cells, while less toxic to A549 and MCF7 cells, and compound <jats:bold>3n<\/jats:bold> as the most toxic derivatve against MDA\u2010MB\u2010231\u2005cell lines, with IC<jats:sub>50<\/jats:sub> value of 5.55\u00b10.56\u2005\u03bcM. Trypan blue staining and colony formation assay showed that compound <jats:bold>3n<\/jats:bold> inhibited the growth of MDA\u2010MB\u2010231 cells and prevented colony formation. Hoechst staining, flow cytometry and western blot analysis revealed that compound <jats:bold>3n<\/jats:bold> induced caspase\u2010dependent apoptosis in MDA\u2010MB\u2010231 cells. Conclusively, compound <jats:bold>3n<\/jats:bold> was demonstrated to be a potential anti\u2010cancer lead compound for further investigation.<\/jats:p>","DOI":"10.1002\/cbdv.202300208","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T10:50:19Z","timestamp":1679655019000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and Evaluation of Piperazine\u2010Tethered Derivatives of Alepterolic Acid as Anticancer Agents"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-4461","authenticated-orcid":false,"given":"Zi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Chemical Biology and Pharmaceutical Engineering School of Chemistry and Chemical Engineering Anhui University of Technology  Ma'anshan Anhui 243002 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NP00022A"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.20156"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2009.03.007"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr900019j"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-019-0270-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12228"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NP00079D"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202002836"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5800"},{"key":"e_1_2_9_10_1","first-page":"136","article-title":"\u2018Structure of the diterpenoid alepterolic acid from Aleuritopteris argentea\u2019","volume":"6","author":"Ageta H.","year":"1962","journal-title":"Proc. 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