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Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity

Record type: Article

The NF-kB transcription factor plays a key role in the regulation of apoptosis by modulating expression of a wide range of cell death control molecules. NF-kB also plays an important role in human diseases by promoting inappropriate cell survival. Small molecule inhibitors of NF-kB are therefore likely to provide novel therapeutic opportunities. Sulfasalazine (SFZ) is a synthetic anti-inflammatory comprising an aminosalicylate, 5-amino salicylic acid (5-ASA), linked to an antibiotic, sulfapyridine (SPY). SFZ, but not 5-ASA or SPY, inhibits activation of NF-kB. We synthesised a small number of SFZ analogues and determined their ability to inhibit NF-kB activity and promote apoptosis in chronic lymphocytic leukaemia and hepatic stellate cells, where NF-kB plays an important role in cell survival. Remarkably, 3 of the 6 analogues synthesised were significantly more effective (up to 8-fold) inhibitors of NF-kB dependent transcription and this increased activity was associated with enhanced apoptosis. Therefore, it is possible to readily improve the NF-kB inhibiting activity of SFZ and analogues of SFZ may be attractive therapeutic agents for malignancies and chronic liver disease where NF-kB is thought to play a significant role.

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Citation

Habens, F., Srinivasan, N., Oakley, F., Mann, D.A., Ganesan, A. and Packham, G. (2005) Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity Apoptosis, 10, (3), pp. 481-491. (doi:10.1007/s10495-005-1877-0).

More information

Published date: 2005
Keywords: apoptosis, chronic lymphocytic leukaemia, fibrosis, hepatic stellate cell, NF-kB, sulfasalazine

Identifiers

Local EPrints ID: 27081
URI: http://eprints.soton.ac.uk/id/eprint/27081
ISSN: 1360-8185
PURE UUID: d66bfaf4-505c-4acd-a8c4-61df9df4b3d0

Catalogue record

Date deposited: 26 Apr 2006
Last modified: 17 Jul 2017 16:05

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