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The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH\/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF<jats:sub>3<\/jats:sub>, OCF<jats:sub>3<\/jats:sub>, F) on the <jats:italic>meta<\/jats:italic>\u2010 of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding <jats:italic>ortho<\/jats:italic>\u2010 and <jats:italic>para<\/jats:italic>\u2010substituted barbituric acid derivatives. Mechanism investigation implied that the <jats:bold>1c<\/jats:bold> could increase the ROS and MDA level, decrease the ratio of GSH\/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.<\/jats:p>","DOI":"10.1002\/cbdv.202100809","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T03:59:45Z","timestamp":1640059185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3840-2086","authenticated-orcid":false,"given":"Yue","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Wen","family":"Mu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Qingdao Vland Biotech INC  3 Chunyang road Qingdao Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u2010Min","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Liaocheng University  1 Hunan Street Liaocheng Shandong 252059 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"W.\u2005S. 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