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| Content Provider | PubMed Central |
|---|---|
| Author | Villagomez, Rodrigo Rajni, Hatti-kaul Sterner, Olov Almanza, Giovanna Linares-pastén, Javier A. |
| Editor | Tajmir-riahi, Heidar-ali |
| Copyright Year | 2015 |
| Abstract | The nuclear factor κB (NF-κB) is a promising target for drug discovery. NF-κB is a heterodimeric complex of RelA and p50 subunits that interact with the DNA, regulating the expression of several genes; its dysregulation can trigger diverse diseases including inflammation, immunodeficiency, and cancer. There is some experimental evidence, based on whole cells studies, that natural sesquiterpene lactones (Sls) can inhibit the interaction of NF-κB with DNA, by alkylating the RelA subunit via a Michael addition. In the present work, 28 natural and semisynthetic pseudoguianolides were screened as potential inhibitors of NF-κB in a biochemical assay that was designed using pure NF-κB heterodimer, pseudoguianolides and a ~1000 bp palindromic DNA fragment harboring two NF-κB recognition sequences. By comparing the relative amount of free DNA fragment to the NF-κB – DNA complex, in a routine agarose gel electrophoresis, the destabilizing effect of a compound on the complex is estimated. The results of the assay and the following structure-activity relationship study, allowed the identification of several relevant structural features in the pseudoguaianolide skeleton, which are necessary to enhance the dissociating capacity of NF-κB–DNA complex. The most active compounds are substituted at C-3 (α-carbonyl), in addition to having the α-methylene-γ-lactone moiety which is essential for the alkylation of RelA. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0115819 |
| Starting Page | 115819 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 1 |
| Volume Number | 10 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2015-01-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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