1,2,4-Thiadiazolidine derivative inhibits nuclear transcription factor-kappaB and its dependent genes activation but induces apoptosis

International Journal of Cancer. Journal International Du Cancer
P MannaS K Manna

Abstract

The 1,2,4-thiadiazolidine derivatives have been shown to be involved in several biological responses such as anti-bacterial, anti-fungal, anti-tubercular and local anaesthetic activities. In our study, we have synthesized some new 5-substitutedarylimino-2-N-substitutedphenyl-3-oxo-1,2,4-thiadiazolidine and tested for anti-inflammatory 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-kappaB), a key transcription factor involved in all forms of inflammation. P(3)-25 inhibited TNF-induced NF-kappaB activation as detected by gel shift assay and dependent reporter gene expression. It inhibited IkappaBalpha degradation, IkappaB kinase activation and p65 nuclear translocation. P(3)-25 inhibited TNF-induced Cox2 expression. It inhibited NF-kappaB 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-inflammator...Continue Reading

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Citations

Jun 17, 2006·Journal of Clinical Immunology·Yashin SreenivasanSunil K Manna
Feb 6, 2010·The Journal of Biological Chemistry·Sunil K MannaChitta Sureshkumar
Aug 31, 2010·Bioorganic & Medicinal Chemistry Letters·Shamileh FouladdelEbrahim Azizi
May 12, 2009·Biochemical Pharmacology·Pongali B RaghavendraSunil K Manna
Jun 22, 2016·Apoptosis : an International Journal on Programmed Cell Death·Raveendra B MokhamatamSunil K Manna

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