title: Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies.
abstract: Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ, UK. r.vilar@imperial.ac.uk.
authors.forename: Juliet
authors.initials: J
authors.lastname: Collins
authors.forename: Agostino
authors.initials: A
authors.lastname: Cilibrizzi
authors.forename: Marina
authors.initials: M
authors.lastname: Fedorova
authors.forename: Gillian
authors.initials: G
authors.lastname: Whyte
authors.forename: Lok Hang
authors.initials: LH
authors.lastname: Mak
authors.forename: Inna
authors.initials: I
authors.lastname: Guterman
authors.forename: Robin
authors.initials: R
authors.lastname: Leatherbarrow
authors.forename: Rudiger
authors.initials: R
authors.lastname: Woscholski
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilar
mesh_terms: D000818:Animals; D001692:Biological Transport; D060326:Chemistry Techniques, Synthetic; D003619:Dansyl Compounds / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010539:Permeability; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010848:Picolinic Acids / Q000737:chemistry*; D014638:Vanadates / Q000737:chemistry*
chemical_list: D003619:Dansyl Compounds; D004791:Enzyme Inhibitors; D008024:Ligands; D009942:Organometallic Compounds; D010848:Picolinic Acids; D014638:Vanadates; D010744:Phosphoric Monoester Hydrolases; C030614:picolinic acid