ABSTRACT
We report the synthesis and characterisation of new, highly fluorescent, zinc complexes of bis(thiosemicarbazone) ligands incorporating extended aromatic backbones which are cytotoxic at levels comparable to cisplatin; cellular fluorescence imaging studies suggest these cause cell death by disruption of mitochondria.
Subject(s)
Carcinoma/drug therapy , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Thiosemicarbazones/chemistry , Zinc/chemistry , Apoptosis/drug effects , Carcinoma/pathology , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Lethal Dose 50 , Microscopy, Confocal , Mitochondria/drug effects , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis , Spectrometry, Fluorescence , Toxicity TestsABSTRACT
New M(II) bis(thiosemicarbazonato) complexes (M = Ni(II), Cu(II) and Zn(II)) featuring allyl groups at the exocyclic nitrogens have been synthesised. The complexes were characterised in solution by spectroscopic methods and their solid state structures determined by single crystal X-ray diffraction using synchrotron radiation. The Zn(II) complex was found to be intrinsically fluorescent and soluble in biocompatible media. The uptake of this Zn(II) complex in HeLa, MCF-7 and IGROV cancer cells was monitored by fluorescence microscopies (epi- and confocal fluorescence imaging). The radiolabelling to (64)Cu(II) bis(thiosemicarbazonato) complex was performed cleanly by transmetallation from the corresponding Zn(II) species using (64)Cu(OAc)(2).