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

Jonathan R. Dilworth, Sofia I. Pascu, Philip A. Waghorn, Daniela Vullo, Simon R. Bayly, Martin Christlieb, Xin Sun, Claudiu T. Supuran

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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 64Cu and 99mTc 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.
Original languageEnglish
Pages (from-to)4859-4873
JournalDalton Transactions
Volume44
Issue number11
Early online date25 Feb 2015
DOIs
Publication statusPublished - 21 Mar 2015

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Carbonic Anhydrases
Sulfonamides
Acetazolamide
Imaging techniques
Rhenium
Indium
X ray crystallography
Technetium
Porphyrins
Tumor Biomarkers
Synchrotrons
Radioisotopes
Molecular structure
Zinc
Tumors
Copper
Protein Isoforms
Derivatives

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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. / Dilworth, Jonathan R.; Pascu, Sofia I.; Waghorn, Philip A.; Vullo, Daniela; Bayly, Simon R.; Christlieb, Martin; Sun, Xin; Supuran, Claudiu T.

In: Dalton Transactions , Vol. 44, No. 11, 21.03.2015, p. 4859-4873.

Research output: Contribution to journalArticle

Dilworth, Jonathan R. ; Pascu, Sofia I. ; Waghorn, Philip A. ; Vullo, Daniela ; Bayly, Simon R. ; Christlieb, Martin ; Sun, Xin ; Supuran, Claudiu T. / 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. In: Dalton Transactions . 2015 ; Vol. 44, No. 11. pp. 4859-4873.
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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 64Cu and 99mTc 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.",
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