TY - JOUR
T1 - Preliminary anti-cancer photodynamic therapeutic in vitro studies with mixed-metal binuclear ruthenium(ii)-vanadium(iv) complexes
AU - Holder, Alvin A.
AU - Taylor, Patrick
AU - Magnusen, Anthony R.
AU - Moffett, Erick T.
AU - Meyer, Kyle
AU - Hong, Yiling
AU - Ramsdale, Stuart E.
AU - Gordon, Michelle
AU - Stubbs, Javelyn
AU - Seymour, Luke A.
AU - Acharya, Dhiraj
AU - Weber, Ralph T.
AU - Smith, Paul F.
AU - Dismukes, G. Charles
AU - Ji, Ping
AU - Menocal, Laura
AU - Bai, Fengwei
AU - Williams, Jennie L.
AU - Cropek, Donald M.
AU - Jarrett, William L.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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 51V 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.
AB - 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 51V 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.
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U2 - 10.1039/c3dt50547b
DO - 10.1039/c3dt50547b
M3 - Article
C2 - 23783642
AN - SCOPUS:84881138731
VL - 42
SP - 11881
EP - 11899
JO - Dalton Transactions
JF - Dalton Transactions
SN - 1477-9226
IS - 33
ER -