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: Alvin A Holder, Patrick Taylor, Anthony R Magnusen, Erick T Moffett, Kyle Meyer, Yiling Hong, Stuart E Ramsdale, Michelle Gordon, Javelyn Stubbs, Luke A Seymour, Dhiraj Acharya, Ralph T Weber, Paul F Smith, G Charles Dismukes, Ping Ji, Laura Menocal, Fengwei Bai, Jennie L Williams, Donald M Cropek, William L Jarrett
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 42 Issue 33 Pg. 11881-99 (Sep 07 2013) ISSN: 1477-9234 [Electronic] England
• PMID: 23783642 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Organometallic Compounds
• Photosensitizing Agents
• Vanadium
• Ruthenium

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Electrochemical Techniques
• Humans
• Molecular Structure
• Organometallic Compounds (chemical synthesis, chemistry, pharmacology)
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Ruthenium (chemistry)
• Structure-Activity Relationship
• Vanadium (chemistry)