Synthesis and Characterization of Novel 2-Amino-Chromene-Nitriles that Target Bcl-2 in Acute Myeloid Leukemia Cell Lines

The anti-apoptotic protein Bcl-2 is a well-known and attractive therapeutic target for cancer. In the present study the solution-phase T3P-DMSO mediated efficient synthesis of 2-amino-chromene-3-carbonitriles from alcohols, malanonitrile and phenols is reported. These novel 2-amino-chromene-3-carbonitriles showed cytotoxicity in human acute myeloid leukemia (AML) cell lines. Compound 4g was found to be the most bioactive, decreasing growth and increasing apoptosis of AML cells. Moreover, compound 4g (at a concentration of 5 µM) increased the G2/M and sub-G1 (apoptosis) phases of AML cells. The AML cells treated with compound 4g exhibited decreased levels of Bcl-2 and increased levels of caspase-9. In silico molecular interaction analysis showed that compound 4g shared a similar global binding motif with navitoclax (another small molecule that binds Bcl-2), however compound 4g occupies a smaller volume within the P2 hot spot of Bcl-2. The intermolecular π-stacking interaction, direct electrostatic interactions, and docking energy predicted for 4g in complex with Bcl-2 suggest a strong affinity of the complex, rendering 4g as a promising Bcl-2 inhibitor for evaluation as a new anticancer agent.     

Production and optimization of carotenoid-enriched dried distiller’s grains with solubles by <Emphasis Type="Italic">Phaffia rhodozyma</Emphasis> and <Emphasis Type="Italic">Sporobolomyces roseus</Emphasis> fermentation of whole stillage

Whole stillage—a co-product of grain-based ethanol—is used as an animal feed in the form of dried distiller’s grain with solubles (DDGS). Since animals cannot synthesize carotenoids and animal feed is generally poor in carotenoids, about 30–120 ppm of total carotenoids are added to animal feed to improve animal health, enhance meat color and quality, and increase vitamin A levels in milk and meat. The main objective of this study was to produce carotenoid (astaxanthin and β-carotene)-enriched DDGS by submerged fermentation of whole stillage. Mono- and mixed cultures of red yeasts, Phaffia rhodozyma (ATCC 24202) and Sporobolomyces roseus (ATCC 28988), were used to produce astaxanthin and β-carotene. Media optimization was carried out in shake flasks using response surface methodology (RSM). Macro ingredients, namely whole stillage, corn steep liquor and glycerol, were fitted to a second-degree polynomial in RSM. Under optimized conditions, astaxanthin and β-carotene yields in mixed culture and P. rhodozyma monoculture were 5 and 278, 97, and 275 μg/g, respectively, while S. roseus produced 278 μg/g of β-carotene. Since the carotenoid yields are almost twice the quantity used in animal feed, the carotenoid-enriched DDGS has potential application as “value-added animal feed or feed blends.”     

Isolation, screening and identification of bacterial strains for degradation of predigested distillery wastewater

Three bacterial isolates from the activated sludge of a distillery wastewater treatment plant identified as Xanthomonas fragariae, Bacillus megaterium and Bacillus cereus were found to remove COD and colour from anaerobically digested distillery wastewater in the range of 55 to 68% and 38 to 58% respectively.