1,2,4-thiadiazolidine derivative inhibits nuclear transcription factor-κB and its dependent genes activation but induces apoptosis
✍ Scribed by Paresh Manna; Krishnan K. Narang; Sunil K. Manna
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- French
- Weight
- 703 KB
- Volume
- 113
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The 1,2,4-thiadiazolidine derivatives have been shown to be involved in several biological responses such as anti-bacterial, antifungal, anti-tubercular and local anaesthetic activities. In our study, we have synthesized some new 5-substitutedarylimino-2-Nsubstitutedphenyl-3-oxo-1,2,4-thiadiazolidine and tested for antiinflammatory and anti-tumor activities. The 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-Oxo-1,2,4-thiadiazolidine (P 3 -25) showed anti-inflammatory activity as it inhibited different inflammatory inducers mediated nuclear transcription factor kappa B (NF-B), a key transcription factor involved in all forms of inflammation. P 3 -25 inhibited TNF-induced NF-B activation as detected by gel shift assay and dependent reporter gene expression. It inhibited IB␣ degradation, IB kinase activation and p65 nuclear translocation. P 3 -25 inhibited TNF-induced Cox2 expression. It inhibited NF-B activation in human epithelial and T cells. Unlike other substitutary derivatives, P 3 -25 was a potent inducer of apoptosis as it induced cell death, caspase-dependent PARP cleavage, ROI generation and lipid peroxidation. Overall our results suggest that P 3 -25 derivative exerts anti-inflammatory and anti-tumor activities, which may have a role in designing such drugs.