Combinatorial Synthesis of Tetrasubstituted Alkenes and Related Compounds with Potential Anticancer Activity.

Objective: In search of efficient anticancer agents, we aimed at the design and synthesis of a library of tetrasubstituted alkenes. These are structural analogues of tamoxifen, one of the widely used anticancer therapeutics.

Methods: Our small organic compound library was prepared via a chemical synthesis in the solution using the Larock three-component coupling reaction, which is known to tolerate diverse functional groups.

Discovery of new inhibitors of nuclease MRE11.

MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors MU147 and MU1409. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-the-art inhibitor mirin.

Practical considerations for the optimization of in situ mineralization of perfluorocarboxylic acids and polyfluoroalkyl substances using persulfate oxidation.

Military bases and airports are often contaminated by per- and polyfluoroalkyl substances (PFAS) due to the repeated use of aqueous film forming foams (AFFFs) from decades of training exercises, equipment testing, and extinguishing of fuel- and solvent-based fires. Pump-and-treat systems combined with sorption processes are common ex situ remediation strategies; however, they can be expensive and may require decades of operation, particularly at sites where long-term diffusion and desorption of contaminants are the primary release processes. Alternatively, in situ chemical oxidation is an effective remediation strategy in which oxidants (e.

Unique and Common Agonists Activate the Insect Juvenile Hormone Receptor and the Human AHR.

Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the fly Drosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes.

Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium sp.