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The compounds demonstrated antiproliferative effects with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 116.92 to 549.73\u00a0\u00b5M. Seven compounds (\n                    <jats:bold>6c<\/jats:bold>\n                    ,\n                    <jats:bold>6f<\/jats:bold>\n                    ,\n                    <jats:bold>6h<\/jats:bold>\n                    ,\n                    <jats:bold>6i<\/jats:bold>\n                    ,\n                    <jats:bold>7b<\/jats:bold>\n                    ,\n                    <jats:bold>7e<\/jats:bold>\n                    , and\n                    <jats:bold>7f<\/jats:bold>\n                    ) exhibited promising antiproliferative activities with IC\n                    <jats:sub>50<\/jats:sub>\n                    values below 140\u00a0\u00b5M in both MDA\u2010MB\u2010231 and MCF\u20107 cancer cell lines. Compound\n                    <jats:bold>7f<\/jats:bold>\n                    demonstrated the highest antiproliferative effect with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 116.92\u00a0\u00b5M in MDA\u2010MB\u2010231 and 124.72\u00a0\u00b5M in MCF\u20107, with an acceptable cytotoxicity profile in normal HUVEC cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 208.41\u00a0\u00b5M); thus, immunomodulatory effects of\n                    <jats:bold>7f<\/jats:bold>\n                    on checkpoint signaling were further evaluated. Compound\n                    <jats:bold>7f<\/jats:bold>\n                    showed a dose\u2010dependent increase of TIGIT, PD\u20101, and LAG\u20103 expression in CD3\n                    <jats:sup>+<\/jats:sup>\n                    T cells. These changes may enhance responsiveness to checkpoint\u2010targeted therapies while reflecting complex regulation of T\u2010cell function. In silico target fishing and molecular docking reflect calpain as a probable target for\n                    <jats:bold>7f<\/jats:bold>\n                    , while DFT analysis indicates electrophilic and nucleophilic positions within\n                    <jats:bold>7f<\/jats:bold>\n                    may help its interaction with the target. Molecular dynamics (MD) simulation supports strong binding of\n                    <jats:bold>7f<\/jats:bold>\n                    with binding energy (\u221222.259\u00a0\u00b1\u00a04.71\u00a0kcal mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    ).\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71611","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:07:32Z","timestamp":1787753252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on Synthesis, Antiproliferative Properties, Immunomodulatory Effects, and Anti\u2010Breast Cancer Activity of New \u0394\n                    <sup>2<\/sup>\n                    \u2010Pyrazoline\u20101\n                    <i>H<\/i>\n                    \u20101,2,3\u2010Triazole Derivatives"],"prefix":"10.1002","volume":"23","author":[{"given":"Sadiq 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