Synthesis, structural characterization and biological studies of novel mixed ligand Ag(I) complexes with triphenylphosphine and aspirin or salicylic acid

• Published in: Inorganica Chimica Acta Vol. 375; no. 1; pp. 114 - 121
• Main Authors: Poyraz, M., Banti, C.N., Kourkoumelis, N., Dokorou, V., Manos, M.J., Simčič, M., Golič-Grdadolnik, S., Mavromoustakos, T., Giannoulis, A.D., Verginadis, I.I., Charalabopoulos, K., Hadjikakou, S.K.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2011
• Subjects: Aspirin; Bioinorganic chemistry; Crystal structures; Cytotoxic activity; Silver(I) complexes; STD 1H NMR; STD 1H NMR; Crystal structures; Aspirin; Bioinorganic chemistry; Silver(I) complexes; Cytotoxic activity
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2011.04.032

Two new mixed ligand silver(I) complexes of formula {[Ag(tpp)3(asp)](dmf)} (1) (aspH=o-acetylsalicylic acid and tpp=tri-phenylphosphine) and [Ag(tpp)2(o-Hbza)] (2) (o-HbzaH=o-hydroxy-benzoic acid) were synthesized and characterized. Complexes 1 and 2 were tested for their in vitro cytotoxic activity. The influence of 1 and 2 against lipoxygenase (LOX) was kinetically and theoretically studied. The binding of 1 and 2 towards LOX was also investigated by Saturation Transfer Difference (STD) 1H NMR experiments. [Display omitted] ► Synthesis of new silver(I) complexes with triphenylphosphine and aspirin or salicylic acid. ► New complexes which can bind to LOX modulating its function. ► Cytostatic activity in relation to LOX inhibition activity caused by the complexes. Two new mixed ligand silver(I) complexes of formulae {[Ag(tpp)3(asp)](dmf)} (1) (aspH=o-acetylsalicylic acid and tpp=triphenylphosphine) and [Ag(tpp)2(o-Hbza)] (2) (o-HbzaH=o-hydroxy-benzoic acid) were synthesized and characterized by elemental analyses, spectroscopic techniques and X-ray crystallography at ambient conditions. Three phosphorus and one carboxylic oxygen atoms from a de-protonated aspirin ligand in complex 1 and two phosphorus and two carboxylic oxygen atoms from a chelating o-Hbza anion in complex 2 form a tetrahedral geometry around Ag(I) ions in both complexes. Complexes 1 and 2 and the silver(I) nitrate, tpp, aspNa and o-HbzaH were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS), human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblasts (MRC-5) cells with Thiazolyl Blue Tetrazolium Bromide (MTT) assay. For both cell lines 1 and 2 were found to be more active than cisplatin. Additionally, 1 and 2 exhibit lower activity on cell growth proliferation of MRC-5 cells. The type of LMS cell death caused by 1 and 2 were evaluated in vitro by use of flow cytometry assay. The results show that at concentrations of 1.5 and 1.9μΜ of complex 1, 44.1% and 69.4%, respectively of LMS cells undergo programmed cell death (apoptosis). When LMS cells were treated with 1.6 and 2.3μM of 2, LMS cells death was by 29.6% and 81.3%, respectively apoptotic. Finally, the influence of the complexes 1 and 2, upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The binding of 1 and 2 towards LOX was also investigated by Saturation Transfer Difference (STD) 1H NMR experiments.