Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.

We report the discovery of small molecules that target the RNA tertiary structure of self-splicing group II introns and display potent antifungal activity against yeasts, including the major public health threat . High-throughput screening efforts against a yeast group II intron resulted in an inhibitor class which was then synthetically optimized for enhanced inhibitory activity and antifungal efficacy. The most highly refined compounds in this series display strong, gene-specific antifungal activity against .

Simple and Efficient Synthesis of -Succinimidyl-4-[F]fluorobenzoate ([F]SFB)-An Important Intermediate for the Introduction of Fluorine-18 into Complex Bioactive Compounds.

-succinimidyl-[F]fluorobenzoate ([F]SFB) is commonly prepared through a three-step procedure starting from [F]fluoride ion. A number of methods for the single-step radiosynthesis of [F]SFB have been introduced recently, including the radiofluorination of diaryliodonium salts and the Cu-mediated F-fluorination of pinacol aryl boronates and aryl tributyl stannanes, but they still have the drawbacks of lengthy product purification procedures. In the present work, two approaches for the direct labeling of [F]SFB from diaryliodonium (DAI) salt () and pinacol aryl boronate () are evaluated, with a major focus on developing a fast and simple SPE-based purification procedure.

MDM2 up-regulates the energy metabolism in NSCLC in a p53-independent manner.

Although an E3 ligase MDM2 is the major negative regulator of the p53 tumor suppressor, a growing body of evidence suggests its p53-independent oncogenic properties. In particular, MDM2 has been shown to regulate serine metabolism independently of p53 status in several types of neoplasia, including NSCLC. Using the GSEA approach and publicly available molecular data on NSCLC tumors, our bioinformatics data suggest that MDM2 affects a number of metabolic genes, particularly those encoding components of the electron transport chain (ETC).

20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells.

20-Hydroxyecdysone (20E) is an arthropod steroid hormone that possesses a number of beneficial pharmacological activities in humans, including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties, etc. While several studies have explored the anabolic activity of 20E in muscle cells, they have concentrated on its effects on myofibril size, protein biosynthesis intensity, and myostatin expression, without assessing energy metabolism. In this research, we have demonstrated that 20E boosts both catabolism and anabolism, coupling energy-producing and biosynthetic metabolic processes in mouse myoblasts and fibroblasts in the same way.

Evaluation of chelating agents based on pyridine-azacrown compounds HPATA, PATAM, and HPATPA for Ga and Lu.

In this article, we present the synthesis and characterization of three macrocyclic chelators, HPATA, PATAM, and HPATPA, based on a pyridine-azacrown compound. Their complexation with Ga and Lu has been thoroughly investigated using MALDI TOF MS, H NMR spectroscopy, radiolabeling studies, and experiments in vitro with fetal bovine serum and a 1000-fold molar excess of HEDTA. Our studies have shown that the chelators HPATA and HPATPA form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with HPATA and HPATPA after 30 min, respectively).