Crystal structure of 4,5-di-bromo-phenanthrene.

The synthesis and crystal structure of the title compound, C14H8Br2, is described. The mol-ecule is positioned on a twofold rotation axis and the asymmetric unit consists of half a mol-ecule with the other half being generated by symmetry. The presence of two large bromine atoms in the bay region significantly distorts the mol-ecule from planarity and the mean planes of the two terminal rings of the phenanthrene system are twisted away from each other by 28.51 (14)°. The torsion angle between the two C-Br bonds is 74.70 (14)° and the distance between the two Br atoms is 3.2777 (13) Å. The mol-ecules pack in layers in the crystal, with the centroids of the central rings of the phenanthrene units in adjacent layers separated by a distance of 4.0287 (10) Å. These centroids are shifted by 2.266 (6) Šrelative to each other, indicating slippage in the stacking arrangement. Furthermore, the distance between the centroids of the terminal and central rings of the phenanthrene units in adjacent layers is slightly shorter at 3.7533 (19) Å. While all of the mol-ecules within each layer are oriented in the same direction, those in adjacent layers are oriented in the opposite direction, leading to anti-parallel stacks.

HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via ß-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation.

Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of ß-site APP cleaving enzyme-1 (BACE1). In addition, PIs induced ß-amyloid production, indicative of increased BACE1-mediated APP processing, in rodent neuroglial cultures and human APP-expressing Chinese hamster ovary cells. Inhibition of BACE1 activity protected against neuronal damage. Finally, ARVs administered to mice and SIV-infected macaques resulted in neuronal damage and BACE1 up-regulation in the central nervous system. These findings implicate a subset of PIs as potential mediators of neurodegeneration in HIV-associated neurocognitive disorders.