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Photo-activated metallotherapeutics: copper(I) or silver(I) mixed ligand complexes with 2-mercaptopyrimidine and triphenylphosphine

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Abstract

Five photosensitive, copper(I) or silver(I) mixed ligand complexes with 2-mercaptopyrimidine (pmtH) and triphenylphosphine (tpp) of formulae [CuCl(tpp)2(pmtH)] (1), {[Cu(tpp)(pmt)]2 0.5(MeOH)} (2), [CuSH(tpp)2(pmtH)] (3), [Cu(tpp)2(pmt)] (4), and [AgCl(tpp)2(pmtH)] (5) were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS), human breast adenocarcinoma cells (MCF-7) normal fibroblasts (MRC-5), before and after UV-C irradiation, using MTT assay. The incubation time (curve) for complexes with cells and irradiation time, were also studied. The type of LMS cell death caused by the complexes was also evaluated by flow cytometry assay. The results show that at concentration of 1.2–9.5 μM of 1–5, 35–98 % of LMS cells undergo programed cell death (apoptosis). The light sensitivity of the complexes is discussed in relation with their biologic activity. All complexes presented significant cytotoxic activity, which has been enhanced by photoactivation.

Graphical Abstract

Five photosensitive, complexes of formulae [CuCl(tpp)2(pmtH)] (1), {[Cu(tpp)(pmt)]2 0.5(MeOH)} (2), [CuSH(tpp)2(pmtH)] (3), [Cu(tpp)2(pmt)] (4), and [AgCl(tpp)2(pmtH)] (5) (pmtH = 2-mercaptopyrimidine, tpp = triphenylphosphine) were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS), before and after UV-C irradiation. The cytotoxicity of 1, 4, and 5 was increased by 37.54, 24.4, and 28.2 %, respectively, compared to the corresponding one of the non-irradiated complexes.

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Authors and Affiliations

  1. Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece

    Α. Velalopoulou, G. K. Batsala & S. K. Hadjikakou

  2. Medical Physics Laboratory, Medical School, University of Ioannina, Ioannina, Greece

    N. Kourkoumelis

  3. Department of Experimental Physiology, Medical School, University of Ioannina, Ioannina, Greece

    Α. Velalopoulou, S. Karkabounas & A. Evangelou

Authors
  1. Α. Velalopoulou
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  2. G. K. Batsala
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  3. N. Kourkoumelis
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  4. S. Karkabounas
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  5. A. Evangelou
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  6. S. K. Hadjikakou
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Correspondence to S. K. Hadjikakou.

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Velalopoulou, Α., Batsala, G.K., Kourkoumelis, N. et al. Photo-activated metallotherapeutics: copper(I) or silver(I) mixed ligand complexes with 2-mercaptopyrimidine and triphenylphosphine. Med Chem Res 22, 2260–2265 (2013). https://doi.org/10.1007/s00044-012-0219-3

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  • DOI: https://doi.org/10.1007/s00044-012-0219-3

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