RESUMO
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.
Assuntos
Carcinoma/tratamento farmacológico , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Tiossemicarbazonas/química , Zinco/química , Apoptose/efeitos dos fármacos , Carcinoma/patologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Dose Letal Mediana , Microscopia Confocal , Mitocôndrias/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Espectrometria de Fluorescência , Testes de ToxicidadeRESUMO
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).