On the motion of hairy black holes in Einstein-Maxwell-dilaton theories

Starting from the static, spherically symmetric black hole solutions in massless Einstein-Maxwell-dilaton (EMD) theories, we build a "skeleton" action, that is, we phenomenologically replace black holes by an appropriate effective point particle action, which is well suited to the formal treatment of the many-body problem in EMD theories. We find that, depending crucially on the value of their scalar cosmological environment, black holes can undergo steep "scalarization" transitions, inducing large deviations to the general relativistic two-body dynamics, as shown, for example, when computing the first post-Keplerian Lagrangian of EMD theories

Using EPR To Compare PEG-<i>branch</i>-nitroxide “Bivalent-Brush Polymers” and Traditional PEG Bottle–Brush Polymers: Branching Makes a Difference

Attachment of poly­(ethylene glycol) (PEG) to polymeric nanostructures is a general strategy for sterically shielding and imparting water solubility to hydrophobic payloads. In this report, we describe direct graft-through polymerization of branched, multifunctional macromonomers that possess a PEG domain and a hydrophobic nitroxide domain. Electron paramagnetic resonance (EPR) spectroscopy was used to characterize microenvironments within these novel nanostructures. Comparisons were made to nitroxide-labeled, traditional bottle-brush random and block copolymers. Our results demonstrate that bivalent bottle-brush polymers have greater microstructural homogeneity compared to random copolymers of similar composition. Furthermore, we found that compared to a traditional brush polymer, the branched-brush, “pseudo-alternating” microstructure provided more rotational freedom to core-bound nitroxides, and greater steric shielding from external reagents. The results will impact further development of multivalent bottle-brush materials as nanoscaffolds for biological applications

Structural Elucidation and Synthesis of Eudistidine A: An Unusual Polycyclic Marine Alkaloid that Blocks Interaction of the Protein Binding Domains of p300 and HIF-1α

Low oxygen environments are a hallmark of solid tumors, and transcription of many hypoxia-responsive genes needed for survival under these conditions is regulated by the transcription factor HIF-1 (hypoxia-inducible factor 1). Activation of HIF-1 requires binding of its α-subunit (HIF-1α) to the transcriptional coactivator protein p300. Inhibition of the p300/HIF-1α interaction can suppress HIF-1 activity. A screen for inhibitors of the protein binding domains of p300 (CH1) and HIF-1α (C-TAD) identified an extract of the marine ascidian <i>Eudistoma</i> sp. as active. Novel heterocyclic alkaloids eudistidines A (<b>1</b>) and B (<b>2</b>) were isolated from the extract, and their structures assigned by spectroscopic analyses. They contain an unprecedented tetracyclic core composed of two pyrimidine rings fused with an imidazole ring. Eudistidine A (<b>1</b>) was synthesized in a concise four-step sequence featuring a condensation/cyclization reaction cascade between 4-(2-aminophenyl)­pyrimidin-2-amine (<b>3</b>) and 4-methoxy-phenylglyoxal (<b>4</b>), while eudistidine B (<b>2</b>) was synthesized in a similar fashion with glyoxylic acid (<b>5</b>) in place of <b>4</b>. Naturally occurring eudistidine A (<b>1</b>) effectively inhibited CH1/C-TAD binding with an IC₅₀ of 75 μM, and synthetic <b>1</b> had similar activity. The eudistidine A (<b>1</b>) scaffold, which can be synthesized in a concise, scalable manner, may provide potential therapeutic lead compounds or molecular probes to study p300/HIF-1α interactions and the role these proteins play in tumor response to low oxygen conditions. The unique structural scaffolds and functional group arrays often found in natural products make these secondary metabolites a rich source of new compounds that can disrupt critical protein–protein binding events

Efficient Synthesis of 1,9-Substituted Benzo[<i>h</i>][1,6]naphthyridin-2(1<i>H</i>)‑ones and Evaluation of their <i>Plasmodium falciparum</i> Gametocytocidal Activities

A novel three-component, two-step, one-pot nucleophilic aromatic substitution (S_NAr)–intramolecular cyclization–Suzuki coupling reaction was developed for the synthesis of benzo­[<i>h</i>]­[1,6]­naphthyridin-2­(1<i>H</i>)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual parasites using a growth inhibition assay and gametocytes using a viability assay