التفاصيل البيبلوغرافية
| العنوان: |
Development of a novel furocoumarin derivative inhibiting NF-κB dependent biological functions: Design, synthesis and biological effects |
| المؤلفون: |
Borgatti, Monica1, Chilin, Adriana2, Piccagli, Laura1, Lampronti, Ilaria1, Bianchi, Nicoletta1, Mancini, Irene1, Marzaro, Giovanni2, Francesco dall’Acqua2, Guiotto, Adriano2 adriano.guiotto@unipd.it, Gambari, Roberto1 gam@unife.it |
| المصدر: |
European Journal of Medicinal Chemistry. Oct2011, Vol. 46 Issue 10, p4870-4877. 8p. |
| مصطلحات موضوعية: |
*PSORALENS, *NF-kappa B, *GENE expression, *CYSTIC fibrosis, *INTERLEUKIN-8, *TUMOR necrosis factors, *ELECTROPHORESIS, *POLYMERASE chain reaction |
| مستخلص: |
Abstract: Nuclear Factor kappaB (NF-κB) plays a very important role in the control of gene expression and is deeply involved in several human pathologies. Accordingly, molecules targeting NF-κB dependent biological functions are considered of great interest. Virtual screening of furocoumarin libraries against NF-κB p50 allowed to rank compounds in respect to their expected ability to bind NF-κB and the identified compound might be considered for the development of analogs to be tested for biological activity on inhibition of NF-κB/DNA complex formation. The data reported in the present paper suggest that, following this approach, the best ranked compounds identified by virtual screening (a) strongly bind in silico to NF-κB and (b) efficiently inhibit the molecular interactions between 32P-labeled NF-κB double stranded DNA and p50 or p50/p65 complex. These data allowed to develop a novel lead of great interest for inhibiting NF-κB dependent biological functions. This novel molecule (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus, exhibits high efficiency in inhibiting NF-κB/DNA interactions. In addition, we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF-α treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that compound 2 might find an important place in the set of molecules of interest for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis. [Copyright &y& Elsevier] |
| قاعدة البيانات: |
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