{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:07:01Z","timestamp":1768525621345,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Laboratories Programme, National Laboratory for Drug Research and Development","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}]},{"DOI":"10.13039\/501100012550","name":"National Research, Development and Innovation Fund","doi-asserted-by":"publisher","award":["ANN 149481"],"award-info":[{"award-number":["ANN 149481"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["FWF 10.55776\/PIN1280424"],"award-info":[{"award-number":["FWF 10.55776\/PIN1280424"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We report the synthesis and biological characterization of N-heterocyclic carbene (NHC) complexes with gold(I), silver(I), copper(I), and palladium(II) metal centers, and 3-(2,6-diisopropyl-phenyl) imidazolinium- and imidazolium-based ligands, including their biscarbene complexes, along with metal complexes of 4-(S)-tert-butyl-imidazolinium-derived carbenes carrying various substituents in position 1. Compared to the imidazolium complexes, the corresponding imidazolinium complexes displayed superior cytotoxicity against the Mes-Sa uterine sarcoma cell line, while the biscarbene complexes exhibited greatly enhanced cytotoxicity with nanomolar activity. The ABCB1-overexpressing multidrug-resistant sublines of Mes-Sa demonstrated only marginal resistance to monocarbene imidazolinium complexes lacking a 4-(S)-tert-butyl group, whereas significant resistance was observed for all other complexes, with its extent further influenced by the nature of the metal center. Probing a subset of the complexes confirmed their strong cytotoxicity against the CST murine breast cancer cell line and its cisplatin-resistant variant, with little or no cross-resistance observed. Within a defined subset, compounds triggered apoptosis, and intracellular ROS production was consistently induced by the copper complexes. Collectively, these results indicate that imidazolinium-based metal NHCs are promising anticancer drug candidates, with copper and silver centers standing out for their potent cytotoxicity and evasion of both ABCB1-mediated and cisplatin resistance.<\/jats:p>","DOI":"10.3390\/ijms262311382","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:46:18Z","timestamp":1764067578000},"page":"11382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imidazolinium-Based NHC\u2013Metal Complexes Overcome Both Cancer Multidrug Resistance and Cisplatin Resistance In Vitro"],"prefix":"10.3390","volume":"26","author":[{"given":"M\u00e1rton","family":"Szl\u00e1vik","sequence":"first","affiliation":[{"name":"Servier Research Institute of Medicinal Chemistry, Z\u00e1hony Utca 7, H-1031 Budapest, Hungary"},{"name":"Hevesy Gy\u00f6rgy PhD School of Chemistry, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/A, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Haffaressas","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"},{"name":"Doctoral School of Biology, Institute of Biology, E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/C, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9ka","family":"Mandel","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanni","family":"Fekecs","sequence":"additional","affiliation":[{"name":"Servier Research Institute of Medicinal Chemistry, Z\u00e1hony Utca 7, H-1031 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-8139","authenticated-orcid":false,"given":"\u00c1gota","family":"Ap\u00e1ti","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Paczal","sequence":"additional","affiliation":[{"name":"Servier Research Institute of Medicinal Chemistry, Z\u00e1hony Utca 7, H-1031 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7675-3864","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Kotschy","sequence":"additional","affiliation":[{"name":"Servier Research Institute of Medicinal Chemistry, Z\u00e1hony Utca 7, H-1031 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-7827","authenticated-orcid":false,"given":"Gergely","family":"Szak\u00e1cs","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"},{"name":"Center for Cancer Research, Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-3531","authenticated-orcid":false,"given":"Szil\u00e1rd","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, H-1117 Budapest, Hungary"},{"name":"National Laboratory for Drug Research and Development, H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216233","DOI":"10.1016\/j.ccr.2024.216233","article-title":"An updated overview on nitrogen-rich azole-based gold coordination complexes as potent anticancer agents","volume":"523","author":"Ghorbanpour","year":"2025","journal-title":"Coord. 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