The Disorazole Z Family of Highly Potent Anticancer Natural Products from Sorangium cellulosum: Structure, Bioactivity, Biosynthesis, and Heterologous Expression.

Myxobacteria serve as a treasure trove of secondary metabolites. During our ongoing search for bioactive natural products, a novel subclass of disorazoles termed disorazole Z was discovered. Ten disorazole Z family members were purified from a large-scale fermentation of the myxobacterium Sorangium cellulosum So ce1875 and characterized by electrospray ionization-high-resolution mass spectrometry (ESI-HRMS), X-ray, nuclear magnetic resonance (NMR), and Mosher ester analysis.

Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes vascular inflammation.

Objective: Glucocorticoid-induced leucine zipper (GILZ) represents an anti-inflammatory mediator, whose downregulation has been described in various inflammatory processes. Aim of our study was to decipher the regulation of GILZ in vascular inflammation.

Approach And Results: Degenerated aortocoronary saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1, CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished GILZ protein and mRNA levels compared to healthy veins (n = 23).

Identification by high-throughput in silico screening of radio-protecting compounds targeting the DNA-binding domain of the tumor suppressor p53.

Therapies targeting p53 mostly concentrate on (re)activation of the p53 protein, to further induce apoptosis in cancer cells. In the present investigations, the focus was on the identification of small molecules that block the DNA-binding domain of p53 and thus inhibit its function. Using high-throughput in silico screening of approximately 300,000 compounds, we identified eight putatively interacting with the DNA-binding domain of p53.