{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:17:28Z","timestamp":1791569848748,"version":"4.3.4"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Gda\u0144sk under the \u2018Excellence Initiative\u2014Research University\u2019 program and the Statutory Activity of the Medical University of Gda\u0144sk","award":["ST 01-50023\/0004931\/513\/513\/0\/2023"],"award-info":[{"award-number":["ST 01-50023\/0004931\/513\/513\/0\/2023"]}]},{"name":"Medical University of Gda\u0144sk under the \u2018Excellence Initiative\u2014Research University\u2019 program and the Statutory Activity of the Medical University of Gda\u0144sk","award":["DEC-2\/2021\/IDUB\/V.6\/Si"],"award-info":[{"award-number":["DEC-2\/2021\/IDUB\/V.6\/Si"]}]},{"name":"Gda\u0144sk University of Technology","award":["ST 01-50023\/0004931\/513\/513\/0\/2023"],"award-info":[{"award-number":["ST 01-50023\/0004931\/513\/513\/0\/2023"]}]},{"name":"Gda\u0144sk University of Technology","award":["DEC-2\/2021\/IDUB\/V.6\/Si"],"award-info":[{"award-number":["DEC-2\/2021\/IDUB\/V.6\/Si"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Recently, there has been great interest in metallopharmaceuticals as potential anticancer agents. In this context, presented studies aim to synthesize and evaluate of two copper(II) complexes derived from phthalazine- and imidazoline-based ligands against on three human cancer cell lines: cervix epithelial cell line (HeLa), breast epithelial-like adenocarcinoma (MCF-7), and triple\u2013negative breast epithelial cancer cell line (MDA-MB-231), as well as non-tumorigenic cell line (HDFa). Moreover their antimicrobial, and antioxidant properties were assessed. Methods: The synthetized compounds\u2014both free ligands L1, L2, L3 and copper(II) complexes C1 and C2\u2014were characterized by elemental analysis, infrared spectroscopy. Additionally, a single-crystal X-ray diffraction studies we performed for free ligand L3 and its copper(II) complex C2. The stability of Cu(II)-complexes C1 and C2 was evaluated by UV-Vis spectroscopy. The cytotoxic potency of free ligands and their copper(II) complexes was estimated on HeLa, MCF-7, MDA-MB-231, as well as non-cancerous HDFa by use of an MTT assay after 48 h of incubation. Moreover, the antimicrobial activity of ligands L1 and L3 and their copper(II) complexes C1 and C2 was evaluated using reference strains of the following bacteria and yeasts: Staphylococcus aureus, Escherichia coli, and Candida albicans. The free radical scavenging properties of free ligands L1, L3 and the corresponding copper(II) complexes C1, C2 was tested with two colorimetric methods\u2014ABTS, DPPH, and reduction ability assay (FRAP). Additionally, the ADME webtool was used to assess the drug-likeness of the synthesized compounds, as well as their physicochemical and pharmacokinetic properties. Results: Copper(II) complex C2 exhibited antitumor properties towards MDA-MB-231 compared with Cisplatin (cancer cell viability rate of 23.6% vs. 22.5%). At a concentration of 200 \u03bcg\/mL, complexes C1 and C2 were less cytotoxic than the reference Cisplatin against a normal, non-cancerous skin fibroblast cell line (HDFa). According to in vitro tests, C2 reduced the viability of HeLa, MCF-7, and MDA-MB-231 cells by about 57.5\u201381.2%. It was evident that all compounds were devoid of antibacterial or antifungal activity. In vitro assays revealed that a moderate antiradical effect was observed for free ligand L1 containing phthalazin-1(2H)-imine in the ABTS radical scavenging assay (IC50 = 23.63 \u00b5g\/mL). Conclusions: The anticancer studies revealed that the most potent compound was copper(II) complex C2 bearing a phthalazin-1(2H)-one scaffold. None of the tested compounds showed antimicrobial or antifungal activity. This feature seems to be beneficial in terms of their potential uses as anticancer agents in the future. In vitro antiradical assays revealed that a moderate antioxidant effect was observed only for free ligand L1 containing phthalazin-1(2H)-imine.<\/jats:p>","DOI":"10.3390\/ph18030375","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:02:13Z","timestamp":1741240933000},"page":"375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, Structure, and Stability of Copper(II) Complexes Containing Imidazoline-Phthalazine Ligands with Potential Anticancer Activity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-1198","authenticated-orcid":false,"given":"\u0141ukasz","family":"Balewski","sequence":"first","affiliation":[{"name":"Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-2723","authenticated-orcid":false,"given":"Iwona","family":"Inkielewicz-St\u0119pniak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gen. D\u0119binki 7, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gdaniec","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 8, 61-614 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-0105","authenticated-orcid":false,"given":"Katarzyna","family":"Turecka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-5380","authenticated-orcid":false,"given":"Anna","family":"Hering","sequence":"additional","affiliation":[{"name":"Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2422-0203","authenticated-orcid":false,"given":"Anna","family":"Ordyszewska","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Chemistry and Advanced Materials Centers, Gda\u0144sk University of Technology, Narutowicza 11\/12, 80-233 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-9229","authenticated-orcid":false,"given":"Anita","family":"Kornicka","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hill, D.P., Harper, A., Malcolm, J., McAndrews, M.S., Mockus, S.M., Patterson, S.E., Reynolds, T., Baker, E.J., Bult, C.J., and Chesler, E.J. (2019). Cisplatin-Resistant triple-negative breast cancer subtypes: Multiple mechanisms of resistance. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6278-9"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2217\/pgs-2017-0117","article-title":"Triple-Negative breast cancer and the potential for targeted therapy","volume":"18","author":"Jhan","year":"2017","journal-title":"Pharmacogenomics"},{"key":"ref_3","first-page":"1","article-title":"Triple negative breast cancer\u2014An overview","volume":"2013","author":"Aysola","year":"2013","journal-title":"Hered. 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