title: Synthesis and cytotoxicity studies of new dimethylamino-functionalised and aryl-substituted titanocene anti-cancer agents.
abstract: From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated aryl species [p-N,N-dimethylanilinyl lithium, p-anisyl lithium and 4-lithio-benzo[1.3]dioxole (2a-c)], the corresponding lithium cyclopentadienide intermediates 4a-c were formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised and aryl-substituted titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 54, 45 and 26microM for titanocenes 5a, b and c, respectively. The most cytotoxic titanocene in this paper, 5c is approximately 10 times less cytotoxic than cis-platin, which showed an IC50 value of 3.3microM, when tested on the LLC-PK cell line, but approximately 100 times better than titanocene dichloride.
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, The UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Clara
authors.initials: C
authors.lastname: Pampillón
authors.forename: James
authors.initials: J
authors.lastname: Claffey
authors.forename: Katja
authors.initials: K
authors.lastname: Strohfeldt
authors.forename: Matthias
authors.initials: M
authors.lastname: Tacke
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004123:Dimethylamines / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D011789:Quantum Theory; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D004123:Dimethylamines; D009942:Organometallic Compounds; C013108:metallocene; C406884:titanocene; C034516:dimethylamine