title: Preliminary anti-cancer photodynamic therapeutic in vitro studies with mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes.
abstract: We report the synthesis and characterisation of mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes, which were used as potential photodynamic therapeutic agents for melanoma cell growth inhibition. The novel complexes, [Ru(pbt)2(phen2DTT)](PF6)2·1.5H2O 1 (where phen2DTT = 1,4-bis(1,10-phenanthrolin-5-ylsulfanyl)butane-2,3-diol and pbt = 2-(2'-pyridyl)benzothiazole) and [Ru(pbt)2(tpphz)](PF6)2·3H2O 2 (where tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) were synthesised and characterised. Compound 1 was reacted with [VO(sal-L-tryp)(H2O)] (where sal-L-tryp = N-salicylidene-L-tryptophanate) to produce [Ru(pbt)2(phen2DTT)VO(sal-L-tryp)](PF6)2·5H2O 4; while [VO(sal-L-tryp)(H2O)] was reacted with compound 2 to produce [Ru(pbt)2(tpphz)VO(sal-L-tryp)](PF6)2·6H2O 3. All complexes were characterised by elemental analysis, HRMS, ESI MS, UV-visible absorption, ESR spectroscopy, and cyclic voltammetry, where appropriate. In vitro cell toxicity studies (with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay) via dark and light reaction conditions were carried out with sodium diaqua-4,4',4'',4''' tetrasulfophthalocyaninecobaltate(II) (Na4[Co(tspc)(H2O)2]), [VO(sal-L-tryp)(phen)]·H2O, and the chloride salts of complexes 3 and 4. Such studies involved A431, human epidermoid carcinoma cells; human amelanotic malignant melanoma cells; and HFF, non-cancerous human skin fibroblast cells. Both chloride salts of complexes 3 and 4 were found to be more toxic to melanoma cells than to non-cancerous fibroblast cells, and preferentially led to apoptosis of the melanoma cells over non-cancerous skin cells. The anti-cancer property of the chloride salts of complexes 3 and 4 was further enhanced when treated cells were exposed to light, while no such effect was observed on non-cancerous skin fibroblast cells. ESR and (51)V NMR spectroscopic studies were also used to assess the stability of the chloride salts of complexes 3 and 4 in aqueous media at pH 7.19. This research illustrates the potential for using mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes to fight skin cancer.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Southern Mississippi, 118 College Drive, #5043, Hattiesburg, Mississippi 39406-0001, USA. alvin.holder@usm.edu
authors.forename: Alvin A
authors.initials: AA
authors.lastname: Holder
authors.forename: Patrick
authors.initials: P
authors.lastname: Taylor
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Magnusen
authors.forename: Erick T
authors.initials: ET
authors.lastname: Moffett
authors.forename: Kyle
authors.initials: K
authors.lastname: Meyer
authors.forename: Yiling
authors.initials: Y
authors.lastname: Hong
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Ramsdale
authors.forename: Michelle
authors.initials: M
authors.lastname: Gordon
authors.forename: Javelyn
authors.initials: J
authors.lastname: Stubbs
authors.forename: Luke A
authors.initials: LA
authors.lastname: Seymour
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Acharya
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Weber
authors.forename: Paul F
authors.initials: PF
authors.lastname: Smith
authors.forename: G Charles
authors.initials: GC
authors.lastname: Dismukes
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Laura
authors.initials: L
authors.lastname: Menocal
authors.forename: Fengwei
authors.initials: F
authors.lastname: Bai
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Williams
authors.forename: Donald M
authors.initials: DM
authors.lastname: Cropek
authors.forename: William L
authors.initials: WL
authors.lastname: Jarrett
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D055664:Electrochemical Techniques; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014639:Vanadium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D014639:Vanadium; D012428:Ruthenium