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Complexes of the type [PdX(PPh 3 )(1)]X [1 = 4-phenyl-3thiosemicarbazide; X = Cl -(2), Br -(3), I -(4), and SCN -(5)] have been synthesized and characterized by elemental analyses and IR, UV/Vis, and 1 H and 13 C NMR spectroscopy. The molecular structure of complex 4 was determined by single-crystal X-ray diffraction. The binding of the complexes with a purine base (guanosine) was investigated by 1 H NMR spectroscopy and mass spectrometry, which showed the com- [a]4499 plexes to coordinate to guanosine through N7. A gel electrophoresis assay demonstrated the ability of 2-5 to cleave DNA plasmid. All the complexes were tested in vitro by means of the MTT assay for their cytotoxicity against two murine cell lines, LM3 (mammary adenocarcinoma) and LP07 (lung adenocarcinoma), and compared with cisplatin. Complexes 2-5 exhibited good cytotoxicity that surpasses that of cisplatin in the case of LM3.

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Abstract:The aim of this study was to construct a nanostructured lipid system as a strategy to improve the in vitro antibacterial activity of copper(II) complexes. New compounds with the general formulae [CuX 2 (INH) 2 ]¨nH 2 O (X = Cl´and n = 1 (1); X = NCS´and n = 5 (2); X = NCO´and n = 4 (3); INH = isoniazid, a drug widely used to treat tuberculosis) derived from the reaction between the copper(II) chloride and isoniazid in the presence or absence of pseudohalide ions (NCS´or NCO´) were synthesized and characterized by infrared spectrometry, electronic absorption spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, elemental analysis, melting points and complexometry with 2,2 1 ,2 11 ,2 111 -(Ethane-1,2-diyldinitrilo)tetraacetic acid (EDTA). The characterization techniques allowed us to confirm the formation of the copper(II) complexes. The Cu(II) complexes were loaded into microemulsion (MEs) composed of 10% phase oil (cholesterol), 10% surfactant [soy oleate and Brij 58 (1:2)] and 80% aqueous phase (phosphate buffer pH = 7.4) prepared by sonication. The Cu(II) complex-loaded MEs displayed sizes ranging from 158.0˘1.060 to 212.6˘1.539 nm, whereas the polydispersity index (PDI) ranged from 0.218˘0.007 to 0.284˘0.034. The antibacterial activity of the free compounds and those that were loaded into the MEs against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922, as evaluated by a microdilution technique, and the cytotoxicity index (IC 50 ) against the Vero cell line (ATCC CCL-81 TM ) were used to calculate the selectivity index (SI). Among the free compounds, only compound 2 (MIC 500 µg/mL) showed activity for S. aureus. After loading the compounds into the MEs, the antibacterial activity of compounds 1, 2 and 3 was significantly increased against E. coli (MIC's 125, 125 and 500 µg/mL, respectively) and S. aureus (MICs 250, 500 and 125 µg/mL, respectively). The loaded compounds were less toxic against the Vero cell line, especially compound 1 (IC 50 from 109.5 to 319.3 µg/mL). The compound 2-and 3-loaded MEs displayed the best SI for E. coli and S. aureus, respectively. These results indicated that the Cu(II) complex-loaded MEs were considerably more selective than the free compounds, in some cases, up to 40 times higher.

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Ag(i) complexes induced apoptosis in triple negative breast cancer cells and were appreciably less cytotoxic against non-tumor cells.