title: Synthesis of sulfonamide conjugates of Cu(II), Ga(III), In(III), Re(V) and Zn(II) complexes: carbonic anhydrase inhibition studies and cellular imaging investigations.
abstract: Carbonic anhydrase IX (CA IX) is currently generating great interest as a marker of tumour hypoxia and a potential chemotherapeutic target. In order to test the principle that a CA IX inhibitor could be used for targeting PET or SPECT metallic radioisotopes to tumours we have prepared a number of conjugates involving aryl-sulfonamides or an acetazolamide derivative linked to a range of copper, indium, rhenium, 99m-technetium and zinc complexes. Radiolabelled (64)Cu and (99m)Tc analogues of the 'cold' Cu and some of the Re complexes were prepared in good radiochemical incorporation. Inhibition of various human carbonic anhydrase isoforms (I, II, IX and XII) was tested with the 'cold', non-radiolabelled complexes, and compared with an acetazolamide standard (AZA). The molecular structure of a new, tri-sulfonated porphyrin-labeled sulfonamide was determined using synchrotron X-ray crystallography.
authors.affiliation: Siemens Oxford Molecular Imaging Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QR, UK. jon.dilworth@chem.ox.ac.uk.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dilworth
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Pascu
authors.forename: Philip A
authors.initials: PA
authors.lastname: Waghorn
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bayly
authors.forename: Martin
authors.initials: M
authors.lastname: Christlieb
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D015687:Cell Hypoxia; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry; D005708:Gallium / Q000737:chemistry; D045325:HCT116 Cells; D006801:Humans; D007204:Indium / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007553:Isotope Labeling; D008665:Metalloporphyrins / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D012211:Rhenium / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry*; D013667:Technetium; D013882:Thiosemicarbazones / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon; D015032:Zinc / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D008665:Metalloporphyrins; D009942:Organometallic Compounds; D013449:Sulfonamides; D013882:Thiosemicarbazones; D007204:Indium; D012211:Rhenium; D013667:Technetium; D003300:Copper; D005708:Gallium; D002256:Carbonic Anhydrases; D015032:Zinc