Anti-cancer characteristics and ototoxicity of platinum(II) amine complexes with only one leaving ligand
نویسندگان
چکیده
Unlike cisplatin, which forms bifunctional DNA adducts, monofunctional platinum(II) complexes bind only one strand of DNA and might target cancer without causing auditory side-effects associated with cisplatin treatment. We synthesized the monofunctional triamine-ligated platinum(II) complexes, Pt(diethylenetriamine)Cl, [Pt(dien)Cl]+, and Pt(N,N-diethyldiethylenetriamine)Cl, [Pt(Et2dien)Cl]+, and the monofunctional heterocyclic-ligated platinum(II) complexes, pyriplatin and phenanthriplatin, and compared their 5'-GMP binding rates, cellular compartmental distribution and cellular viability effects. A zebrafish inner ear model was used to determine if the monofunctional complexes and cisplatin caused hearing threshold shifts and reduced auditory hair cell density. The four monofunctional complexes had varied relative GMP binding rates, but similar cytosolic and nuclear compartmental uptake in three cancer cell lines (A549, Caco2, HTB16) and a control cell line (IMR90). Phenanthriplatin had the strongest effect against cellular viability, comparable to cisplatin, followed by [Pt(Et2dien)Cl]+, pyriplatin and [Pt(dien)Cl]+. Phenanthriplatin also produced the highest hearing threshold shifts followed by [Pt(dien)Cl]+, [Pt(Et2dien)Cl]+, cisplatin and pyriplatin. Hair cell counts taken from four regions of the zebrafish saccule showed that cisplatin significantly reduced hair cell density in three regions and phenanthriplatin in only one region, with the other complexes having no significant effect. Utricular hair cell density was not reduced by any of the compounds. Our results suggest that placing greater steric hindrance cis to one side of the platinum coordinating center in monofunctional complexes promotes efficient targeting of the nuclear compartment and guanosine residues, and may be responsible for reducing cancer cell viability. Also, the monofunctional compounds caused hearing threshold shifts with minimal effect on hair cell density, which suggests that they may affect different pathways than cisplatin.
منابع مشابه
Synthesis and Characterization of New Mercury (II) Complexes with Bidentate Chelating Schiff Base Iminopyridine Ligand
First, Schiff base iminopyridine ligands has been prepared by the condensation between primaryamines, different substituted anilines and active carbonyl group of pyridine carboxaldehyde, thenthe complexes [diiodo (3-ethylphenyl) pyridine-2-yl methylene amine] mercury(II), complex a,[dibromo (2,5-dimethylphenyl) pyridine-2-yl methylene amine] mercury(II) complex b, and[dinitrato bis-(2,6-dimethy...
متن کاملSynthesis and Characterization of Homo and Heterobimetallic Complexes with a Dicompartmental Macrocyclic Ligand Containing Propionitrile Pendent Arms
A binuclear macrocyclic ligand containing dissimilar N(amine)2O2 and N(imine)2O2 coordination sites sharing two phenolic oxygen atoms, was prepared by cyclic condensation of dialdehyde precursor L1H2 with 1,3-diaminopropane. The ligand includes two propionitrile pendant arms on the amine nitrogen atoms. The homobimetallic com...
متن کاملA Survey of Anticancer Effect of Some Five- and Six-Membered Palladium (II) Complexes (Containing Bidentate Phosphorus Ligands) on Caco-2 Colon Cancer Cell Line
Background and Objectives: Transition metal complexes possess a variety of biological and pharmacological activities, such as antitumor, antimicrobial, anti-inflammatory, anti-diabetic, and free radical scavenging. Many studies have been carried out on platinum-based chemotherapy agents, however, most attention has been paid to non-platinum metal-based agents in order to find different metal comp...
متن کاملRhodium, palladium and platinum complexes of tris(pyridylalkyl)amine and tris(benzimidazolylmethyl)amine N4-tripodal ligands.
To investigate the influence of a potentially N4-tripodal amine ligand on the structure and internal exchange processes of its complexes with late transition metals, five rhodium, six palladium and two platinum complexes have been prepared from seven alkyl-bridged N-heterocyclic amine tripodal ligands: tris(2-pyridylmethyl)amine, (2-(2-pyridylethyl))bis(2-pyridylmethyl)amine, bis(2-(2-pyridylet...
متن کاملAnti-tumor activity of Fe (III), Co(II) and Pd(II) complexes of N3-{phenyl [(4-pyridylcarbonyl)amino]methyl}
An anti-tumor compound as N3-{phenyl [(4-pyridylcarbonyl) amino] methyl} weresynthesized and identified (NPPA). Fe (III), Co(II) and Pd(II) metal complexes of this ligand preparedby reaction of chloride salt of Fe (III), Co(II) and Pd(II) with NPPA in dry acetonitrile. Identification andCharacterization of the ligand was performed by FT-IR, 1H-NMR spectroscopy and elemental an...
متن کامل