{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:57:46Z","timestamp":1785527866935,"version":"3.56.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"DOI":"10.1007\/s00210-026-05745-4","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T01:50:02Z","timestamp":1785203402000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel copper\u2013phenothiazine\u2013amino acid complexes exhibit selective anticancer activity via induction of apoptosis and cell cycle arrest in HepG2 cells"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9501-851X","authenticated-orcid":false,"given":"Sally M.","family":"Tamim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-1289","authenticated-orcid":false,"given":"Emad El","family":"Zayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6403-7345","authenticated-orcid":false,"given":"Sherif Abdelaziz","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6303-5126","authenticated-orcid":false,"given":"Azza A.","family":"Shoukry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"5745_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106171","volume":"129","author":"AHH Ahmed","year":"2022","unstructured":"Ahmed AHH, Mohamed MFA, Allam RM, Nafady A, Mohamed SK, Gouda AE, Beshr EAM (2022) Design, synthesis, and molecular docking of novel pyrazole-chalcone analogs of lonazolac as 5-LOX, iNOS and tubulin polymerization inhibitors with potential anticancer and anti-inflammatory activities. Bioorg Chem 129:106171. https:\/\/doi.org\/10.1016\/j.bioorg.2022.106171","journal-title":"Bioorg Chem"},{"issue":"19","key":"5745_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25194566","volume":"25","author":"NA Al Zahrani","year":"2020","unstructured":"Al Zahrani NA, El-Shishtawy RM, Elaasser MM, Asiri AM (2020) Synthesis of novel chalcone-based phenothiazine derivatives as antioxidant and anticancer agents. Molecules (Basel, Switzerland) 25(19):4566. https:\/\/doi.org\/10.3390\/molecules25194566","journal-title":"Molecules (Basel, Switzerland)"},{"key":"5745_CR3","unstructured":"American Cancer Society (2025)\u00a0Cancer facts & figures 2025. American Cancer Society. https:\/\/www.cancer.org\/research\/cancer-facts-statistics\/all-cancer-facts-figures\/cancer-facts-figures-2025.html"},{"key":"5745_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105556","volume":"119","author":"H Amiri Rudbari","year":"2022","unstructured":"Amiri Rudbari H, Saadati A, Aryaeifar M, Blacque O, Cuevas-Vicario JV, Cabral R, Raposo LR, Fernandes AR (2022) Platinum(II) and copper(II) complexes of asymmetric halogen-substituted [NN\u2032O] ligands: synthesis, characterization, structural investigations, and antiproliferative activity. Bioorg Chem 119:105556. https:\/\/doi.org\/10.1016\/j.bioorg.2021.105556","journal-title":"Bioorg Chem"},{"issue":"12","key":"5745_CR5","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.31557\/APJCP.2024.25.12.4247","volume":"25","author":"AN Artanti","year":"2024","unstructured":"Artanti AN, Jenie RI, Rumiyati R, Meiyanto E (2024) Hesperidin and diosmin increased cytotoxic activity cisplatin on hepatocellular carcinoma and protect kidney cells senescence. Asian Pac J Cancer Prev 25(12):4247\u20134255. https:\/\/doi.org\/10.31557\/APJCP.2024.25.12.4247","journal-title":"Asian Pac J Cancer Prev"},{"issue":"5","key":"5745_CR6","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.3390\/molecules23051020","volume":"23","author":"MA Baghdadi","year":"2018","unstructured":"Baghdadi MA, Al-Abbasi FA, El-Halawany AM, Aseeri AH, Al-Abd AM (2018) Anticancer profiling for coumarins and related O-naphthoquinones from Mansonia gagei against solid tumor cells in vitro. Molecules 23(5):1020. https:\/\/doi.org\/10.3390\/molecules23051020","journal-title":"Molecules"},{"key":"5745_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2024.122467","volume":"575","author":"SV Barad","year":"2025","unstructured":"Barad SV, Jadeja RN, Butcher RJ (2025) Crystal structure, DFT and Hirshfeld surface analysis of acylpyrazolone based square pyramidal Cu(II) complex: in-vitro anticancer activity. Inorg Chim Acta 575:122467. https:\/\/doi.org\/10.1016\/j.ica.2024.122467","journal-title":"Inorg Chim Acta"},{"key":"5745_CR8","unstructured":"BIOVIA Dassault Syst\u00e8mes (2025) BIOVIA discovery studio visualizer (version 25.1). Dassault Syst\u00e8mes. Landrum, G. (2016). RDKit: Open-source cheminformatics software. GitHub. https:\/\/www.rdkit.org"},{"issue":"7","key":"5745_CR9","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s11243-009-9259-z","volume":"34","author":"C-Y Chen","year":"2009","unstructured":"Chen C-Y, Chen Q-Z, Wang X-F, Liu M-S, Chen YF (2009) Synthesis, characterization, DNA binding properties, and biological activities of a mixed ligand copper (II) complex of ofloxacin. Transit Metal Chem 34(7):757\u2013763","journal-title":"Transit Metal Chem"},{"issue":"6","key":"5745_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065449","volume":"24","author":"S Cibotaru","year":"2023","unstructured":"Cibotaru S, Sandu AI, Nicolescu A, Marin L (2023) Antitumor activity of PEGylated and TEGylated phenothiazine derivatives: structure-activity relationship. Int J Mol Sci 24(6):5449. https:\/\/doi.org\/10.3390\/ijms24065449","journal-title":"Int J Mol Sci"},{"issue":"20","key":"5745_CR11","doi-asserted-by":"publisher","first-page":"5840","DOI":"10.1016\/j.electacta.2010.05.033","volume":"55","author":"MV Colqui Quiroga","year":"2010","unstructured":"Colqui Quiroga MV, Monz\u00f3n LMA, Yudi LM (2010) Interaction of triflupromazine with distearoylphosphatidylglycerol films studied by surface pressure isotherms and cyclic voltammetry at a 1,2-dichloroethane\/water interface. Electrochim Acta 55(20):5840\u20135846. https:\/\/doi.org\/10.1016\/j.electacta.2010.05.033","journal-title":"Electrochim Acta"},{"issue":"4","key":"5745_CR12","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/life11040365","volume":"11","author":"C Colturato-Kido","year":"2021","unstructured":"Colturato-Kido C, Lopes RM, Medeiros HCD, Costa CA, Prado-Souza LFL, Ferraz LS, Rodrigues T (2021) Inhibition of autophagy enhances the antitumor effect of thioridazine in acute lymphoblastic leukemia cells. Life (Basel, Switzerland) 11(4):365. https:\/\/doi.org\/10.3390\/life11040365","journal-title":"Life (Basel, Switzerland)"},{"issue":"8","key":"5745_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11081010","volume":"11","author":"JP Costa","year":"2022","unstructured":"Costa JP, Pinheiro T, Martins MS, Carvalho MFNN, Feliciano JR, Leit\u00e3o JH, Silva RAL, Guerreiro JF, Alves LMC, Cust\u00f3dio I, Cruz J, Marques F (2022) Tuning the biological activity of camphorimine complexes through metal selection. Antibiotics (Basel) 11(8):1010. https:\/\/doi.org\/10.3390\/antibiotics11081010","journal-title":"Antibiotics (Basel)"},{"issue":"12","key":"5745_CR14","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/ng.3421","volume":"47","author":"GM DeNicola","year":"2015","unstructured":"DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC (2015) NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet 47(12):1475\u20131481. https:\/\/doi.org\/10.1038\/ng.3421","journal-title":"Nat Genet"},{"issue":"10","key":"5745_CR15","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.3390\/biom12101360","volume":"12","author":"D Duarte","year":"2022","unstructured":"Duarte D, Vale N (2022) Antipsychotic drug fluphenazine against human cancer cells. Biomolecules 12(10):1360. https:\/\/doi.org\/10.3390\/biom12101360","journal-title":"Biomolecules"},{"key":"5745_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/s12247-023-09745-2","author":"NS Elkholy","year":"2023","unstructured":"Elkholy NS, Hariri MLM, Mohammed HS et al (2023) Lutein and \u03b2-carotene characterization in free and nanodispersion forms in terms of antioxidant activity and cytotoxicity. J Pharm Innov. https:\/\/doi.org\/10.1007\/s12247-023-09745-2","journal-title":"J Pharm Innov"},{"issue":"1","key":"5745_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36089-6","volume":"9","author":"MI Fekry","year":"2019","unstructured":"Fekry MI, Ezzat SM, Salama MM, Alshehri OY, Al-Abd AM (2019) Bioactive glycoalkaloides isolated from Solanum melongena fruit peels with potential anticancer properties against hepatocellular carcinoma cells. Sci Rep 9(1):1746. https:\/\/doi.org\/10.1038\/s41598-018-36089-6","journal-title":"Sci Rep"},{"issue":"8","key":"5745_CR18","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1038\/cdd.2009.44","volume":"16","author":"L Galluzzi","year":"2009","unstructured":"Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Kroemer G (2009) Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ 16(8):1093\u20131107. https:\/\/doi.org\/10.1038\/cdd.2009.44","journal-title":"Cell Death Differ"},{"issue":"2","key":"5745_CR19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.mrgentox.2007.05.011","volume":"633","author":"S Gangopadhya","year":"2007","unstructured":"Gangopadhya S, Karmakar P, Dasgupta U, Chakraborty A (2007) Trifluoperazine stimulates ionizing radiation induced cell killing through inhibition of DNA repair. Mutat Res 633(2):117\u2013125. https:\/\/doi.org\/10.1016\/j.mrgentox.2007.05.011","journal-title":"Mutat Res"},{"issue":"10","key":"5745_CR20","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1016\/j.bmc.2016.04.001","volume":"24","author":"A Ghinet","year":"2016","unstructured":"Ghinet A, Moise IM, Rigo B, Homerin G, Farce A, Dubois J, B\u00eecu E (2016) Studies on phenothiazines: new microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents. Bioorg Med Chem 24(10):2307\u20132317. https:\/\/doi.org\/10.1016\/j.bmc.2016.04.001","journal-title":"Bioorg Med Chem"},{"issue":"1-2","key":"5745_CR21","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1080\/00958972.2023.2296381","volume":"77","author":"MR Graci","year":"2024","unstructured":"Graci MR, Awwadi FF, Dickie DA, Landee CP, Turnbull MM (2024) Synthesis, coordination modes, structures, and magnetic properties of halogen-substituted 2-hydroxypyridine copper(II) chloride coordination compounds. J Coord Chem 77(1\u20132):79\u2013100. https:\/\/doi.org\/10.1080\/00958972.2023.2296381","journal-title":"J Coord Chem"},{"issue":"19","key":"5745_CR22","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1016\/j.biomaterials.2013.03.010","volume":"34","author":"K Han","year":"2013","unstructured":"Han K, Chen S, Chen WH, Lei Q, Liu Y, Zhuo RX, Zhang XZ (2013) Synergistic gene and drug tumor therapy using a chimeric peptide. Biomaterials 34(19):4680\u20134689. https:\/\/doi.org\/10.1016\/j.biomaterials.2013.03.010","journal-title":"Biomaterials"},{"issue":"2","key":"5745_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101012","volume":"297","author":"ASB Heitmann","year":"2021","unstructured":"Heitmann ASB, Zanjani AAH, Klenow MB, Mularski A, S\u00f8nder SL, Lund FW, Boye TL, Dias C, Bendix PM, Simonsen AC, Khandelia H, Nylandsted J (2021) Phenothiazines alter plasma membrane properties and sensitize cancer cells to injury by inhibiting annexin-mediated repair. J Biol Chem 297(2):101012. https:\/\/doi.org\/10.1016\/j.jbc.2021.101012","journal-title":"J Biol Chem"},{"issue":"1-2","key":"5745_CR24","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.bpc.2007.07.001","volume":"130","author":"AB Hendrich","year":"2007","unstructured":"Hendrich AB, Michalak K, Weso\u0142owska O (2007) Phase separation is induced by phenothiazine derivatives in phospholipid\/sphingomyelin\/cholesterol mixtures containing low levels of cholesterol and sphingomyelin. Biophys Chem 130(1\u20132):32\u201340. https:\/\/doi.org\/10.1016\/j.bpc.2007.07.001","journal-title":"Biophys Chem"},{"issue":"18","key":"5745_CR25","doi-asserted-by":"publisher","first-page":"7048","DOI":"10.1039\/D3DT00568A","volume":"52","author":"C \u0130\u00e7sel","year":"2023","unstructured":"\u0130\u00e7sel C, Y\u0131lmaz VT, Ayg\u00fcn M, Erk\u0131sa M, Ulukaya E (2023) Water-soluble copper(II) 5-fluorouracil complexes bearing polypyridyl co-ligands: synthesis, structures, and anticancer activity. Dalton Trans 52(18):7048\u20137058. https:\/\/doi.org\/10.1039\/D3DT00568A","journal-title":"Dalton Trans"},{"key":"5745_CR26","unstructured":"International Agency for Research on Cancer (2024)\u00a0GLOBOCAN 2022: Egypt fact sheet. Global cancer observatory. https:\/\/gco.iarc.who.int\/media\/globocan\/factsheets\/populations\/818-egypt-fact-sheet.pdf. Accessed\u00a0January 2026"},{"issue":"2","key":"5745_CR27","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","volume":"40","author":"G Kroemer","year":"2010","unstructured":"Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40(2):280\u2013293. https:\/\/doi.org\/10.1016\/j.molcel.2010.09.023","journal-title":"Mol Cell"},{"issue":"19\u201324","key":"5745_CR28","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1080\/00958972.2022.2150548","volume":"75","author":"CP Landee","year":"2022","unstructured":"Landee CP, Awwadi FF, Twamley B, Turnbull MM (2022) Coordination chemistry and magnetic properties of copper(II) halide complexes of quinoline. J Coord Chem 75(19\u201324):2616\u20132627. https:\/\/doi.org\/10.1080\/00958972.2022.2150548","journal-title":"J Coord Chem"},{"key":"5745_CR29","unstructured":"Landrum G (2016) RDKit: Open-source cheminformatics"},{"issue":"9","key":"5745_CR30","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrm2239","volume":"8","author":"MC Maiuri","year":"2007","unstructured":"Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8(9):741\u2013752. https:\/\/doi.org\/10.1038\/nrm2239","journal-title":"Nat Rev Mol Cell Biol"},{"key":"5745_CR31","doi-asserted-by":"publisher","unstructured":"Marcheggiani F, Cirilli I, Orlando P, Silvestri S, Vogelsang A, Knott A, Blatt T, Weise JM, Tiano L (2019) Modulation of coenzyme Q10 content and oxidative status in human dermal fibroblasts using HMG-CoA reductase inhibitor over a broad range of concentrations: From mitohormesis to mitochondrial dysfunction and accelerated aging. Aging, 11(9):2565\u20132582. https:\/\/doi.org\/10.18632\/aging.101911","DOI":"10.18632\/aging.101911"},{"issue":"3","key":"5745_CR32","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ijantimicag.2007.10.025","volume":"31","author":"M Martins","year":"2008","unstructured":"Martins M, Dastidar SG, Fanning S, Kristiansen JE, Molnar J, Pag\u00e8s JM, Schelz Z, Spengler G, Viveiros M, Amaral L (2008) Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Agents 31(3):198\u2013208. https:\/\/doi.org\/10.1016\/j.ijantimicag.2007.10.025","journal-title":"Int J Antimicrob Agents"},{"issue":"2","key":"5745_CR33","doi-asserted-by":"publisher","first-page":"185","DOI":"10.2174\/187152009787313837","volume":"9","author":"C Marzano","year":"2009","unstructured":"Marzano C, Pellei M, Tisato F, Santini C (2009) Copper complexes as anticancer agents. Anti-Cancer Agents Med Chem 9(2):185\u2013211. https:\/\/doi.org\/10.2174\/187152009787313837","journal-title":"Anti-Cancer Agents Med Chem"},{"issue":"9","key":"5745_CR34","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.2174\/138945006778226570","volume":"7","author":"K Michalak","year":"2006","unstructured":"Michalak K, Wesolowska O, Motohashi N, Molnar J, Hendrich AB (2006) Interactions of phenothiazines with lipid bilayer and their role in multidrug resistance reversal. Curr Drug Targets 7(9):1095\u20131105. https:\/\/doi.org\/10.2174\/138945006778226570","journal-title":"Curr Drug Targets"},{"key":"5745_CR35","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.saa.2011.11.015","volume":"86","author":"MS Mohamed","year":"2012","unstructured":"Mohamed MS, Shoukry AA, Ali GA (2012) Synthesis and structural characterization of ternary Cu (II) complexes of glycine with 2,2\u2032-bipyridine and 2,2\u2032-dipyridylamine. The DNA-binding studies and biological activity. Spectrochim Acta A Mol Biomol Spectrosc 86:562\u2013570. https:\/\/doi.org\/10.1016\/j.saa.2011.11.015","journal-title":"Spectrochim Acta A Mol Biomol Spectrosc"},{"issue":"16","key":"5745_CR36","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785\u20132791. https:\/\/doi.org\/10.1002\/jcc.21256","journal-title":"J Comput Chem"},{"key":"5745_CR37","volume-title":"Infrared and Raman spectra of inorganic and coordination compounds","author":"K Nakamoto","year":"2009","unstructured":"Nakamoto K (2009) Infrared and Raman spectra of inorganic and coordination compounds, 6th ed. Wiley","edition":"6th ed."},{"key":"5745_CR38","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2147\/DDDT.S119488","volume":"11","author":"U Ndagi","year":"2017","unstructured":"Ndagi U, Mhlongo N, Soliman ME (2017) Metal complexes in cancer therapy - an update from drug design perspective. Drug des Devel Ther 11:599\u2013616. https:\/\/doi.org\/10.2147\/DDDT.S119488","journal-title":"Drug des Devel Ther"},{"key":"5745_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O'Boyle","year":"2011","unstructured":"O\u2019Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open babel: an open chemical toolbox. J Cheminform 3:10. https:\/\/doi.org\/10.1186\/1758-2946-3-33","journal-title":"J Cheminform"},{"issue":"3-4","key":"5745_CR40","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.drudis.2011.01.001","volume":"16","author":"MJ Ohlow","year":"2011","unstructured":"Ohlow MJ, Moosmann B (2011) Phenothiazine: the seven lives of pharmacology\u2019s first lead structure. Drug Discov Today 16(3\u20134):119\u2013131. https:\/\/doi.org\/10.1016\/j.drudis.2011.01.001","journal-title":"Drug Discov Today"},{"issue":"2","key":"5745_CR41","first-page":"439","volume":"61","author":"S Paglin","year":"2001","unstructured":"Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J (2001) A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 61(2):439\u2013444","journal-title":"Cancer Res"},{"key":"5745_CR42","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.biomaterials.2018.04.027","volume":"171","author":"SY Qin","year":"2018","unstructured":"Qin SY, Cheng YJ, Lei Q, Zhang AQ, Zhang XZ (2018) Combinational strategy for high-performance cancer chemotherapy. Biomaterials 171:178\u2013197. https:\/\/doi.org\/10.1016\/j.biomaterials.2018.04.027","journal-title":"Biomaterials"},{"issue":"18","key":"5745_CR43","doi-asserted-by":"publisher","first-page":"14085","DOI":"10.1021\/acs.chemrev.1c00757","volume":"122","author":"R Qing","year":"2022","unstructured":"Qing R, Hao S, Smorodina E, Jin D, Zalevsky A, Zhang S (2022) Protein design: from the aspect of water solubility and stability. Chem Rev 122(18):14085\u201314179. https:\/\/doi.org\/10.1021\/acs.chemrev.1c00757","journal-title":"Chem Rev"},{"issue":"5","key":"5745_CR44","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1007\/s11030-022-10556-9","volume":"27","author":"HO Rasul","year":"2023","unstructured":"Rasul HO, Aziz BK, Ghafour DD, Kivrak A (2023) Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction. Mol Divers 27(5):2273\u20132296. https:\/\/doi.org\/10.1007\/s11030-022-10556-9","journal-title":"Mol Divers"},{"key":"5745_CR45","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1021\/cr400135x","volume":"114","author":"C Santini","year":"2014","unstructured":"Santini C, Pellei M, Gandin V, Porchia M, Tisato F, Marzano C (2014) Advances in copper complexes as anticancer agents. Chem Rev 114:815\u2013862. https:\/\/doi.org\/10.1021\/cr400135x","journal-title":"Chem Rev"},{"issue":"7","key":"5745_CR46","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3390\/cryst13071141","volume":"13","author":"V Sesti","year":"2023","unstructured":"Sesti V, D\u2019Antonio M, Lucotti A, Moretti P, Castagna R, Bertarelli C, Tommasini M (2023) Combining UV-Vis and resonance Raman spectroscopy to characterize molecular aggregation. Crystals 13(7):1141. https:\/\/doi.org\/10.3390\/cryst13071141","journal-title":"Crystals"},{"issue":"12","key":"5745_CR47","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201704007","volume":"30","author":"Z Shen","year":"2018","unstructured":"Shen Z, Song J, Yung BC, Zhou Z, Wu A, Chen X (2018) Emerging strategies of cancer therapy based on ferroptosis. Advanced materials (Deerfield Beach, Fla.) 30(12):e1704007. https:\/\/doi.org\/10.1002\/adma.201704007","journal-title":"Advanced materials (Deerfield Beach, Fla.)"},{"issue":"4","key":"5745_CR48","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1158\/2159-8290.CD-15-0894","volume":"6","author":"CJ Sherr","year":"2016","unstructured":"Sherr CJ, Beach D, Shapiro GI (2016) Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov 6(4):353\u2013367. https:\/\/doi.org\/10.1158\/2159-8290.CD-15-0894","journal-title":"Cancer Discov"},{"issue":"10","key":"5745_CR49","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1007\/s10953-011-9753-8","volume":"40","author":"AA Shoukry","year":"2011","unstructured":"Shoukry AA (2011) Complex formation reactions of promethazine copper(II) and various biologically relevant ligands: synthesis, equilibrium constants, spectroscopic characterization and biological activity. J Solution Chem 40(10):1768\u20131788. https:\/\/doi.org\/10.1007\/s10953-011-9753-8","journal-title":"J Solution Chem"},{"key":"5745_CR50","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s10953-006-9032-2","volume":"35","author":"AA Shoukry","year":"2006","unstructured":"Shoukry AA, Mohamed MM, Shoukry MM (2006) Binary and ternary complexes of copper(ii) involving N, N, N, N-tetramethyl ethylenediamine (Me4en) and various biologically relevant ligands. J Solution Chem 35:853\u2013868","journal-title":"J Solution Chem"},{"issue":"10","key":"5745_CR51","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1007\/s10953-011-9692-3","volume":"40","author":"AA Shoukry","year":"2011","unstructured":"Shoukry AA, Elhakim HKA, Sultan NS, Rashidi FB (2011) Complex formation reactions of promethazine copper(II) and various biologically relevant ligands: Synthesis, equilibrium constants, spectroscopic characterization and biological activity. J Solution Chem 40(10):1796\u20131818. https:\/\/doi.org\/10.1007\/s10953-011-9692-3","journal-title":"J Solution Chem"},{"issue":"1","key":"5745_CR52","first-page":"26","volume":"14","author":"S Shukla","year":"2025","unstructured":"Shukla S (2025) Advances in the study of copper(II) complexes with amino acids: synthesis, characterization, and applications. Int J Sci Res 14(1):26\u201328","journal-title":"Int J Sci Res"},{"issue":"4","key":"5745_CR53","doi-asserted-by":"publisher","first-page":"955","DOI":"10.3390\/ijms20040955","volume":"20","author":"K \u015aroda-Pomianek","year":"2019","unstructured":"\u015aroda-Pomianek K, Michalak K, Palko-\u0141abuz A, Uryga A, \u015awi\u0105tek P, Majkowski M, Weso\u0142owska O (2019) The combined use of phenothiazines and statins strongly affects doxorubicin-resistance, apoptosis, and cox-2 activity in colon cancer cells. Int J Mol Sci 20(4):955. https:\/\/doi.org\/10.3390\/ijms20040955","journal-title":"Int J Mol Sci"},{"issue":"7","key":"5745_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202300450","volume":"20","author":"NS Sultan","year":"2023","unstructured":"Sultan NS, Elhakim HKA, Shoukry AA, Rashidi FB (2023) Synthesis, characterization, and biological evaluation of Cu(II) complexes containing triflupromazine with glycine and histidine. Chem Biodivers 20(7):e202300450. https:\/\/doi.org\/10.1002\/cbdv.202300450","journal-title":"Chem Biodivers"},{"issue":"3","key":"5745_CR55","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1007\/s12013-024-01376-9","volume":"82","author":"NS Sultan","year":"2024","unstructured":"Sultan NS, Shoukry AA, Rashidi FB, Elhakim HKA (2024) Biological applications, in vitro cytotoxicity, cellular uptake, and apoptotic pathway studies induced by ternary Cu(II) complexes involving triflupromazine with biorelevant ligands. Cell Biochem Biophys 82(3):2651\u20132671. https:\/\/doi.org\/10.1007\/s12013-024-01376-9","journal-title":"Cell Biochem Biophys"},{"issue":"2","key":"5745_CR56","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1002\/med.21338","volume":"35","author":"Y Sun","year":"2015","unstructured":"Sun Y (2015) Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures. Med Res Rev 35(2):408\u2013436. https:\/\/doi.org\/10.1002\/med.21338","journal-title":"Med Res Rev"},{"issue":"2","key":"5745_CR57","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","volume":"65","author":"LA Torre","year":"2015","unstructured":"Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87\u2013108. https:\/\/doi.org\/10.3322\/caac.21262","journal-title":"CA Cancer J Clin"},{"issue":"2","key":"5745_CR58","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s10585-023-10202-0","volume":"40","author":"H Xi","year":"2023","unstructured":"Xi H, Wu M, Ma H, Li S, Huang Q, Zhang Y, Xia Y (2023) Repurposing fluphenazine to suppress melanoma brain, lung and bone metastasis by inducing G0\/G1 cell cycle arrest and apoptosis and disrupting autophagic flux. Clin Exp Metastasis 40(2):161\u2013175. https:\/\/doi.org\/10.1007\/s10585-023-10202-0","journal-title":"Clin Exp Metastasis"},{"issue":"W1","key":"5745_CR59","doi-asserted-by":"publisher","first-page":"W271","DOI":"10.1093\/nar\/gkae415","volume":"52","author":"B Ye","year":"2024","unstructured":"Ye B, Tian W, Wang B, Lian J (2024) CASTpFold: computed atlas of surface topography of the universe of protein folds. Nucleic Acids Res 52(W1):W271","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"5745_CR60","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfab064","volume":"13","author":"S Zehra","year":"2021","unstructured":"Zehra S, Cirilli I, Silvestri S, G\u00f3mez-Ruiz S, Tabassum S, Arjmand F (2021) Structure elucidation, in vitro binding studies and ROS-dependent anti-cancer activity of Cu(II) and Zn(II) phthaloylglycinate(phen) complexes against MDA-MB-231 cells. Metallomics 13(11):mfab064. https:\/\/doi.org\/10.1093\/mtomcs\/mfab064","journal-title":"Metallomics"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05745-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05745-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05745-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:16:26Z","timestamp":1785521786000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05745-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":60,"alternative-id":["5745"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05745-4","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"assertion":[{"value":"1 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}