{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:41:45Z","timestamp":1783694505987,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST111-2123-M-259-002"],"award-info":[{"award-number":["MOST111-2123-M-259-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin-based chemotherapy is a common regimen for bladder cancer, a life-threatening cancer with more than 500,000 new cases worldwide annually. Like many other metallodrugs, cisplatin causes severe side effects for its general toxicity. Organoruthenium is known for its structural stability, good anticancer activity, and possible low general toxicity. Here, we have prepared and characterized a series of water-soluble ruthenium-arene complexes with N,N\u2032-chelating ligands: [Ru(II)-\u03b76-arene-(4,4\u2032-(X)2-2,2\u2032-bipyridine)Cl]Cl (arene = p-cymene, X = C4H9 (1), COOH (2), COOCH3 (3), COOC2H5 (4); arene = benzene, X = C4H9 (5), COOCH3 (6), COOC2H5 (7)). These complexes are carefully characterized using single-crystal X-ray diffraction, UV-vis, IR, 1H NMR, and MALDI-TOF MS spectroscopy. Their DFT-calculated structural and thermodynamic properties are consistent with the experimental observations. Biophysicochemical studies of complex interaction with CTDNA and BSA supported by molecular docking simulations reveal suitable properties of 1\u20137 as anticancer agents. Cytotoxicities of 1\u20137 are evaluated on healthy human MCF-10a-breast epithelial and African green monkey Vero cells, and carcinoma human HepG-2-hepatic, T24-bladder, and EAhy-926-endothelial cells. All complexes exhibit much higher cytotoxicity for T24 than cisplatin. Particularly, 1 and 2 are also highly selective toward T24. Fluorescence imaging and flow cytometry demonstrate that 1 and 2 penetrate T24 cell membrane and induce early apoptosis at their respective IC50 concentrations, which ultimately lead to cell death. Statistical analysis suggests that the order of importance for T24 cell antiproliferation is protein binding, Log p, Ru\u2013Cl bond length, while DNA binding is the least important. This study is the first to report the anti-bladder cancer efficacy of Ru-arene-2,2\u2032-bipyridine complexes, and may provide insights for rational design of organoruthenium drugs in the enduring search for new chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/ijms241511896","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"11896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effective and Selective Ru(II)-Arene Complexes Containing 4,4\u2032-Substituted 2,2\u2032 Bipyridine Ligands Targeting Human Urinary Bladder Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-6631","authenticated-orcid":false,"given":"Mathiyan","family":"Muralisankar","sequence":"first","affiliation":[{"name":"Physics Department, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Physics Department, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-032X","authenticated-orcid":false,"given":"Jebiti","family":"Haribabu","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de Atacama, Copayapu 485, Copiapo 1531772, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyue-Chu","family":"Ke","sequence":"additional","affiliation":[{"name":"Physics Department, National Dong Hwa University, Hualien 97401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Fuchs and Ahmedin Jemal","volume":"71","author":"Siegel","year":"2021","journal-title":"Cancer Stat. 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