RESUMO
Three Ru(II)-DMSO complexes (1-3) containing 2-(3-pyrazolyl)pyridine (PzPy), 2-pyrazol-3-ylfuran (PzO), or 2-pyrazol-3-ylthiophene (PzS) ligand, were synthesized and characterized. The monodentate coordination of the heterocyclic pyrazolyl ligand (PzPy) with Ru(II) ion via N atom was confirmed by single crystal X-ray diffraction. Complex 1 could be converted to the known η2-bidentate PzPy complex cis(Cl), cis(S)-[RuCl2(PzPy)(DMSO)2] (4) under reflux conditions. The mechanism underlying binding mode transformation was studied by 1H NMR spectroscopy and density functional theory (DFT) calculations. The binding abilities of the complexes (1-4) with calf-thymus (CT) DNA and bovine serum albumin (BSA) were investigated using spectroscopic and molecular docking techniques. Among the four Ru(II) complexes, complexes 1 and 3 inhibited the long-term proliferation of human breast cancer cells, whereas complexes 2 and 4 did not inhibit their proliferation to a considerable extent. Interestingly, complexes 1 and 3 did not induce significant cell death but rather attenuated the clonogenicity of breast cancer cells by upregulating reactive oxygen species (ROS), endoplasmic reticulum (ER) and autophagic stress.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Dimetil Sulfóxido/análogos & derivados , Dimetil Sulfóxido/farmacologia , Pirazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , DNA/metabolismo , Dimetil Sulfóxido/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Pirazóis/síntese química , Pirazóis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Soroalbumina Bovina/metabolismoRESUMO
A water-soluble Schiff base, 2,3-bis((E)-(2-hydroxy-3-methoxybenzylidene)amino) propanoic acid (ODA) prepared by condensing o-vanillin and DL-2,3-diaminopropionic acid was evaluated as an efficient "turn on" fluorescent chemosensor for the selective recognition of Al3+ and Zn2+ ions in presence of several interfering metal ions (detection limit; for Al3+ = 1.82 nM, Zn2+ = 7.06 nM). The probe also shows a selective chromogenic behavior towards Al3+ and Zn2+ ions that the naked eye can view. The binding stoichiometry was determined using 1H-NMR titration and ESI-MS spectrometry. The sensing mechanism is due to the inhibition of ESIPT and isomerization of -C=N of ODA on complexation with Al3+/Zn2+. The intramolecular hydrogen bonding energy and the critical bond energy in ODA-Al3+/Zn2+ were calculated using QTAIM analysis. The Thin Layer Chromatography (TLC) plates and strip papers loaded with ODA were used to test the practical applications for sensing Al3+ and Zn2+ ions. Moreover, the probe has been used for live-cell imaging to detect Al3+ and Zn2+ ions in hepatoma C3A and human glioblastoma U87 cells.
