0000000000496299
AUTHOR
Andreas Sellmer
Synthesis of Naturally Occurring Pyrazine and Imidazole Alkaloids from Botryllus LeachiRID=?a?ID=?a? Dedicated to Prof. G . Märkl on the occasion of his 75 th birthday
The synthesis of the naturally occurring and biologically active alkaloids 1 and 2, first isolated from the red ascidian Botryllus leachi by Duran et al. [1], is described and the structure proposed for Botryllazine B (1) is confirmed. The analytical data for 2-(p-hydroxybenzoyl)-4-(p-hydroxyphenyl)imidazole (2) are discussed and compared with the literature. With special emphasis of 1H NMR data the tautomerism of aroylimidazolemethanones is described.
HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.
Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We fur…
Class I histone deacetylases regulate p53/NF-κB crosstalk in cancer cells
The transcription factors NF-κB and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytokines promote signaling cascades that lead to the co-regulation of p53 and NF-κB. Consequently, nuclear p53/NF-κB signaling complexes activate NF-κB-dependent survival genes. The 18 histone deacetylases (HDACs) are epigenetic modulators that fall into four classes (I-IV). Inhibitors of histone deacetylases (HDACi) become increasingly appreciated as anti-cancer agents. Based on their effects on p53 and NF-κB, we addressed whether clinically relevant HDACi affect the NF-κB/p53 crosstalk. The chemotherapeutics hydroxyurea, etoposide, an…