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To enhance NIC\u2019s pharmacokinetic and pharmacodynamic characteristics and make it a potential anticancer drug, thirteen NIC-Schiff bases were created by condensation reaction of NIC-amine\n                    <jats:bold>2<\/jats:bold>\n                    with various monocyclic\/bicyclic\/tricyclic aromatic aldehydes\/acetophenone in absolute ethanol. Several spectroscopic methods, such as elemental analysis, IR, \u00b9H NMR, and MS, were used to determine the structures of these novel synthesized compounds. MTT assay was used to assess the target compounds\u2019 activity against prostate cancer cell line (PC-3) and two breast cancer cell lines (MCF-7) and (MDA-MB-231). IC\n                    <jats:sub>50<\/jats:sub>\n                    was determined for the most promising compounds using doxorubicin and NIC as reference standards. Among the compounds examined, the noteworthy compound\n                    <jats:bold>11<\/jats:bold>\n                    exhibited IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 2.85, 4.61, and 7.69 \u00b5M against MCF-7, MDA-MB-231, and PC-3, respectively, whereas, compound\n                    <jats:bold>8<\/jats:bold>\n                    displayed IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 8.70 and 8.20 \u00b5M against MCF-7 and MDA-MB-231, respectively. Using NIC as a reference standard, a mechanistic analysis of the interesting compounds\n                    <jats:bold>8<\/jats:bold>\n                    and\n                    <jats:bold>11<\/jats:bold>\n                    revealed dual inhibitory effect on JAK1 and CDK7 enzymes. They elicited greater amounts of JAK1 inhibition in MCF-7 and MDA-MB-231 (81-85.5%, 53.6-69.18%) than NIC (75.6% and 36.6%, respectively). Surprisingly, compound\n                    <jats:bold>11<\/jats:bold>\n                    inhibits CDK7 more than NIC does on MCF-7 (80.7%) and PC-3 (83.4%) cells. Additionally, compound\n                    <jats:bold>11<\/jats:bold>\n                    produced cell cycle arrest at G2\/M (35.03%) with overexpression of pre-G (20.68%) in contrast to the control (20.95%) and (0.31%), respectively. With respect to the control, compound\n                    <jats:bold>11<\/jats:bold>\n                    performed better than NIC in raising the levels of apoptosis mediators, caspases 1, 3, and 9, in MDA-MB-231 cells by 4.60, 3.03, and 2.69 times, respectively. Like NIC, it also activates caspase 1 in PC-3 cells 3.5 times more than control. According to flow cytometry results,\n                    <jats:bold>11<\/jats:bold>\n                    significantly increased apoptotic cell death from 1.34% to 10.92% and necrotic cell death from 1.05% to 3.47% in comparison to control MCF-7 cells. The docking results of NIC-Schiff bases\n                    <jats:bold>8<\/jats:bold>\n                    and\n                    <jats:bold>11<\/jats:bold>\n                    confirmed the combined in vitro inhibitory effects of the JAK1 and CDK7 enzymes. Compound\n                    <jats:bold>11<\/jats:bold>\n                    establishes a more stable, tightly bound complex with JAK1, as indicated by molecular dynamics.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-33185-2","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:34:02Z","timestamp":1768296842000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel niclosamide-derived Schiff bases as a dual-targeted anticancer agents"],"prefix":"10.1038","volume":"16","author":[{"given":"Magda M. 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