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Bioorg Med Chem Lett. 2007 Sep 15;17(18):5032-5. Epub 2007 Jul 19.

Inhibition of carbonic anhydrase isozymes I, II and IX with benzenesulfonamides containing an organometallic moiety.

Author information

1
Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Qld 4111, Australia.

Abstract

A novel series of benzenesulfonamides that contain ferrocenyl or ruthenocenyl moieties were synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant carbonic anhydrase (CA) isozymes: hCA I, II and tumour-associated IX (h=human). This manuscript describes the regioselective synthesis of both the 1,4- and 1,5-disubstituted-1,2,3-triazole benzenesulfonamides from ethynylmetallocene substrates. This is the first report describing the covalent attachment of organometallic moieties to the arylsulfonamide (ArSO(2)NH(2)) CA recognition pharmacophore. At hCA I these metallocene derivatives were either nanomolar or low micromolar inhibitors, while against hCA II and IX inhibition in the range of 9.7-80nM and 10.3-85nM, respectively, was observed. The ruthenocenyl derivatives gave superior CA inhibition compared to the ferrocenyl compounds across all three CA isozymes. These compounds constitute a new organometallic class of CA inhibitors with promising biological activity.

PMID:
17681760
DOI:
10.1016/j.bmcl.2007.07.024
[Indexed for MEDLINE]

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