New Boron Containing Acridines: Synthesis and Preliminary Biological Study.

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT).

Proteomics-based scoring of cellular response to stimuli for improved characterization of signaling pathway activity.

Omics technologies focus on uncovering the complex nature of molecular mechanisms in cells and organisms, including biomarkers and drug targets discovery. Aiming at these tasks, we see that information extracted from omics data is still underused. In particular, characteristics of differentially regulated molecules can be combined in a single score to quantify the signaling pathway activity. Such a metric can be useful for comprehensive data interpretation to follow: (1) developing molecular responses in time; (2) potency of a drug on a certain cell culture; (3) ranking the signaling pathway activity in stimulated cells; and (4) integration of the omics data and assay-based measurements of cell viability, cytotoxicity, and proliferation. With recent advances in ultrafast mass spectrometry for quantitative proteomics allowing data collection in a few minutes, proteomics score for cellular response to stimuli can become a fast, accurate, and informative complement to bioassays. Here, we utilized an interquartile-based selection of differentially regulated features and a variety of schemes for quantifying cellular responses to come up with the quantitative metric for total cellular response and pathway activity. Validation was performed using antiproliferative and virus assays and label-free proteomics data collected for cancer cells subjected to drug stimulation.

New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their "Click" Chemistry Reactions for the Conjugation with closo-Dodecaborate Anion.

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. CuI catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption-emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated.