Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.

To gain further insights into the importance of the unsaturated 1,4-ketoaldehyde moiety of ophiobolin A (OpA) for the potency and selectivity observed toward cancer stem cells, several derivatives were synthesized through controlled reduction and oxidations of the unsaturated aldehyde and ketone moieties. Structure elucidation of these new OpA derivatives was achieved through detailed NMR studies and comparison to OpA and known isolated congeners possessing variations in these regions. The relative stereochemistry of the newly generated stereocenters was determined by coupling constants in conjunction with conformational analyses (DFT) of the synthetic derivatives.

Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3.

Background: The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.

Results: In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants.

Novel Flavin Mononucleotide-Functionalized Cerium Fluoride Nanoparticles for Selective Enhanced X-Ray-Induced Photodynamic Therapy.

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.

Syntheses of 3-(2-Nitrovinyl)-indoles, Benzo[]carbazoles, Naphtho[2,1-]carbazoles, and 1-Hydroxy-β-carbolines Lead to Identification of Antiproliferative Compounds Active under Hypoxia.

Herein, we describe a novel reaction between C-2-substituted indoles and 2-nitroacetophenones leading to a variety of indole-containing heterocyclic scaffolds. At 60 °C in AcOH with HSO as catalyst, C-2 aryl indoles give 3-(2-nitrovinyl)-indoles with high or geometric selectivity depending on the type of substrate utilized. These compounds undergo an electrocyclization process in a sealed vial in a microwave apparatus in DMF at 250 °C to give benzo[]carbazoles and naphtho[2,1-]carbazoles depending on whether the C-2 aromatic moiety is phenyl or naphthyl.

Ophiobolin A derivatives with enhanced activities under tumor-relevant acidic conditions.

Glioblastoma (GBM) is the most common form of malignant primary brain tumor and is one of the most lethal cancers. The difficulty in treating GBM stems from its highly developed mechanisms of drug resistance. Our research team has recently identified the fungal secondary metabolite ophiobolin A (OpA) as an agent with significant activity against drug-resistant GBM cells.