Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity
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), 481-491. (doi:10.1007/s10495-005-1877-0).
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Description/Abstract
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.
| Item Type: | Article |
|---|---|
| ISSNs: | 1360-8185 (print) |
| Related URLs: | |
| Keywords: | apoptosis, chronic lymphocytic leukaemia, fibrosis, hepatic stellate cell, NF-kB, sulfasalazine |
| Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QR Microbiology |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair University Structure - Pre August 2011 > School of Chemistry University Structure - Pre August 2011 > School of Medicine > Human Genetics |
| Item ID: | 27081 |
| Date Deposited: | 26 Apr 2006 |
| Last Modified: | 01 Jun 2011 08:52 |
| Contributors: | Habens, F. (Author) Srinivasan, N. (Author) Oakley, F. (Author) Mann, D.A. (Author) Ganesan, A. (Author) Packham, G. (Author) |
| Date: | 2005 |
| Status: | Published |
| Contact Email Address: | G.K.Packham@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/27081 |
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