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The oxime derivatives were synthesized and characterized using\n                    <jats:sup>1<\/jats:sup>\n                    H-NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C-NMR, and mass spectrometry. In vitro cytotoxicity was assessed against C6 (glioma), MCF-7 (breast cancer), and SH-SY5Y (human neuroblastoma) cell lines. Flow cytometry evaluated apoptosis and cell cycle arrest for the lead compound. Molecular docking simulations were performed against CDK6 (PDB: 5L2I) and P-glycoprotein\/ABCB1 (PDB: 7A6E). All derivatives exhibited selective potency against C6 glioma cells. Compound\n                    <jats:bold>14<\/jats:bold>\n                    demonstrated the highest antiproliferative activity (IC\u2085\u2080: 31.23\u00a0\u00b5M) against tumor lines while sparing SH-SY5Y cells. Flow cytometry confirmed that compound\n                    <jats:bold>14<\/jats:bold>\n                    triggers apoptosis and induces cell cycle arrest in C6 cells. Molecular docking predicted the most favorable docking scores for compound\n                    <jats:bold>14<\/jats:bold>\n                    against both CDK6 and P-glycoprotein. Structure\u2013activity relationships (SAR) analysis validates the 4-methylpyrazole core as a viable scaffold for targeted glioma therapy. These results suggest that further functionalization of the O-alkyl oxime moiety merits further investigation as a starting point for potentially brain-penetrant scaffolds, although\n                    <jats:italic>in vivo<\/jats:italic>\n                    and target-level validation are required.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05618-w","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T03:33:43Z","timestamp":1782531223000},"page":"19685-19707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational design of pyrazole\u2013oxime hybrids as dual-targeting agents for glioma and breast cancer brain metastasis"],"prefix":"10.1007","volume":"399","author":[{"given":"Merve","family":"Gul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Abdullah","family":"Alagoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceylan","family":"Hepokur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oztekin","family":"Algul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"5618_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28186521","volume":"28","author":"KS Abdelrahman","year":"2023","unstructured":"Abdelrahman KS, Hassan HA, Abdel-Aziz SA, Marzouk AA, Shams R, Osawa K, Abdel-Aziz M, Konno H (2023) Development and assessment of 1,5-diarylpyrazole\/oxime hybrids targeting EGFR and JNK-2 as antiproliferative agents: a comprehensive study through synthesis, molecular docking, and evaluation. 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