title: Labile ruthenium(ii) complexes with extended phenyl-substituted terpyridyl ligands: synthesis, aquation and anticancer evaluation.
abstract: Ruthenium complexes have been considered as promising substitutes for cisplatin in cancer chemotherapy. However, novel ruthenium-based therapies are faced with some limitations, such as unimpressive cytotoxicity toward solid tumors. Herein, we designed and synthesized phenyl-substituted terpyridyl ruthenium(ii) complexes ([Ru(tpy)(bpy)Cl](+) (Ru1), [Ru(phtpy)(bpy)Cl](+) (Ru2) and [Ru(biphtpy)(bpy)Cl](+) (Ru3)) which exhibited distinctly different anticancer activity. Ru1-Ru3 all underwent moderate aquation in buffer solution and this process was significantly inhibited by high chloride concentration. Cancer cells were found to readily uptake the relatively hydrophobic Ru3, as quantified using inductively coupled plasma mass spectrometry (ICP-MS). Ru1 was found to be non-cytotoxic (IC50 > 100 μM) while Ru3 exhibited very promising cytotoxicity on both two-dimensional (2D) cancer cell monolayers and 3D MCTSs. An antiproliferative assay revealed that Ru3 significantly inhibited cellular DNA replication which ultimately induced apoptosis of cancer cells.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
authors.forename: Huaiyi
authors.initials: H
authors.lastname: Huang
authors.forename: Pingyu
authors.initials: P
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Liangnian
authors.initials: L
authors.lastname: Ji
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002712:Chlorides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D008024:Ligands; D009942:Organometallic Compounds; D014867:Water; D012428:Ruthenium