Synthesis, characterization, antibacterial and antitumoral activities of mononuclear zinc complexes containing tridentate amine based ligands with N3 or N2O donor groups

The synthesis and characterization of the four zinc(II) complexes [Zn(HL1)Cl-2] (1), [Zn(H2L2)Cl-2](2), [Zn(H2L3)Cl-2] (3) and[Zn(H2L4)Cl-2] (4), where HL1 = (bis-2-pyridylmethyl)amine, H2L2 = (2-hydroxybenzyl- 2-pyridylmethyl) amine, H2L3 = N-2[(pyridine-2-ylmethyl)amino)ethanol, H2L4 = 1-[(pyridine-2-ylmethyl)- amino]-propan-2-ol are reported; (3) and (4) are new while (2) was reported previously but its structure had not been determined. The complexes were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic, electrospray ionization mass spectrometry (ESI(+)-MS) and tandem mass spectrometry ESI(+)-MS/MS). X-ray diffraction studies were performed for complexes (1)-(3) revealing the presence of mononuclear structures in the solid state. The X-ray analyses of (1) and (3) demonstrate that HL1 and HL2 act as tridentate ligands, while the ligand H2L2 in (2) is bidentate. The cytotoxic properties of the ligands and of all the complexes were examined using human leukemia THP-1, U937 and Molt-4 cells. Complex (4) exhibited the highest cytotoxicity in this series with an IC50 value of 75 +/- 1 mu mol L (1) against U937 cells. Transmission electron microscopy (TEM) reveals ultrastructural changes typical of apoptotic cells. The induction of apoptosis was confirmed by the annexin V assay. The antimicrobial activity of complexes (1)-(4) was also investigated in vitro against four Gram-positive bacteria (ATCC10832, ATCC25923, COL) and the clinical Staphylococcus aureus isolate LSA88 (SEC/SEF/ TSST-1+). Complex (2) showed the most potent inhibitory activity, reaching almost 100% of inhibition against all strains tested. Morphological investigations using TEM indicate that the antibacterial activity of complex (2) may be associated with the inhibition of cell wall and therefore cell division. (C) 2014 Elsevier B. V. All rights reserved

Modulating the antitumoral activity by the design of new platinum(II) compounds: Synthesis, characterization, DFT, ultrastructure and mechanistic studies

The synthesis, physico-chemical characterization, Density functional theory (DFT) calculation and cytotoxicity against five human tumoral cell lines (THP-1, U937, Molt-4, Colo205 and H460) of four new platinum(II) coordination compounds are reported, i.e. [Pt(HL1)Cl]·H O (1), [Pt(HL2)Cl]·H O (2), [Pt(HL3)Cl]·H O (3) and [Pt(HL4)Cl]·H O (4). The ligands contain N2O donor sets. Furthermore, H2L3 and H2L4 present α and β-naphthyl groups respectively, which are absent in HL1 and H2L2. X-ray diffraction studies were performed for complex (3), indicating the formation of a mononuclear platinum(II) complex. Complexes (3) and (4), which contain α and β-naphthyl groups respectively, have presented lower IC (inhibitory concentration) values than those exhibited by complexes (1) and (2). The mechanism of cell death promoted by complexes (3) and (4) was investigated, suggesting that, toward U937 cell line, the α isomer promotes death by apoptosis and the β isomer by necrosis. Transmission and scanning electron microscopy investigations are in agreement with the loss of mitochondrial membrane potential (ΔΨm) observed by JC-1 mitochondrial potential sensor and indicate that the activity of complex (3) against U937 cell line is mediated by an apoptotic mechanism associated with mitochondrial dysfunction. A quantification of caspases 3, 6, 8 and 9 indicated that both the intrinsic and extrinsic pathways are involved in the apoptotic stimuli. Based on DFT calculations all the Pt(II) complexes present the same coordination environment for the metal centre, indicating that the higher cytotoxic activities exhibited by complexes (3) and (4) are related to the presence of the α and β-naphthyl groups in the ligand structure