Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues

The polyether ionophore salinomycin ( SAL ) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, herein we describe the synthesis of a new class of SAL analogues that combine key modifications at the C1 and C20 positions. The activity of the obtained SAL derivatives was evaluated using primary acute lymphoblastic leukemia, human breast adenocarcinoma and normal mammary epithelial cells. One single- [N,N-dipropyl amide of salinomycin ( 5 a )] and two novel double-modified analogues [N,N-dipropyl amide of C20-oxosalinomycin ( 5 b ) and piperazine amide of C20-oxosalinomycin ( 13 b )] were found to be more potent toward the MDA-MB-231 cell line than SAL or its C20-oxo analogue 2 . When select analogues were tested against the NCI-60 human tumor cell line panel, 4 a [N,N-diethyl amide of salinomycin] showed particular activity toward the ovarian cancer cell line SK-OV-3. Additionally, both SAL and 2 were found to be potent ex vivo against human ER/PR⁺, Her2⁻ invasive mammary carcinoma, with 2 showing minimal toxicity toward normal epithelial cells. The present findings highlight the therapeutic potential of SAL derivatives for select targeting of different cancer types.     

PSA Depletion Induces the Differentiation of Immature Neurons in the Piriform Cortex of Adult Mice

Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.     

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential.     

Influence of sodium alginate and methylcellulose on hydrolysis and physicochemical properties of α-TCP based materials

The effect of the sodium alginate and methylcellulose modifiers on hydrolysis, setting reaction, microstructure, mechanical and in vitro properties of α-TCP based materials was investigated. It was found that the presence of sodium alginate impeded α-TCP hydrolysis to hydroxyapatite, which may have a significant influence on resorbability, biodegradation and biological behavior of biomaterials. There were several reasons for these phenomena, such as: (I) the gelation of sodium alginate in the presence of Ca²⁺, (II) the creation of an organic layer which impedes the diffusion of water molecules to α-TCP and (III) the uptake of water molecules by sodium alginate. The inhibitory effect was not observed for methylcellulose and it was diminished in simulated body fluid. Additionally, it was demonstrated that the examined cements varied in their microstructure, setting times and compressive strengths, depending on the applied kind of a polymer additive. The cement containing sodium alginate had a higher compressive strength (20 ± 8 MPa) than the one with methylcellulose (17 ± 4 MPa) and the one lacking polymer (14 ± 4 MPa). All the developed materials exhibited high bioactivity in vitro.     

Determination of Branched-Chain Amino Acids in Food Supplements and Human Plasma by a CE-MS/MS Method with Enhanced Resolution

In the presented study, a capillary electrophoresis-mass spectrometry method combining high separation efficiency and sensitive detection has been developed and validated, for the first time, to quantify branched chain amino acids (valine, isoleucine, leucine) in commercial food and sport supplement samples and human plasma samples. The separations were performed in a bare fused silica capillary. The background electrolyte was composed of 500 mM formic acid with pH 2.0. The plasma sample pretreatment was realized by simple protein precipitation with acetonitrile. Injection of a short zone of highly basic electrolyte before the sample injection and application of the negative pressure on the separation were accompanied by enhanced resolution of the isobaric amino acids—isoleucine and leucine. The developed method was characterized by favorable validation parameters, such as linearity (r² > 0.99), accuracy and precision, the limit of detection, lower limit of quantification, or robustness. These parameters were more than sufficient for the quantification of branched chain amino acids in various samples. The determined concentrations of branched chain amino acids in food and sports supplements were in very good agreement with the content declared by the manufacturer. The investigated concentrations of branched chain amino acids were in the range 294.68–359.24 µM for valine, 91.76–95.67 µM for isoleucine, and 196.78–251.24 µM for leucine. These concentrations fall within the physiological limits. The developed CE-MS/MS method represents a suitable alternative to traditional approaches used in branched chain amino acid quality control and bioanalysis.     

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

There is a need for new, safer, and more effective agents to treat cancer. Cytostatics that have transition metals at their core have attracted renewed interest from scientists. Researchers are attempting to use chemotherapeutics, such as cisplatin, in combination therapy (i.e., in order to enhance their effectiveness). Moreover, studies are being carried out to modify molecules, by developing them into multinuclear structures, linking different compounds to commonly used drugs, or encapsulating them in nanoparticles to improve pharmacokinetic parameters, and increase the selectivity of these drugs. Therefore, we attempted to organize recent drug findings that contain palladium and platinum atoms in their structures.     

Synthesis and spectral properties of colloidal Nd doped NaYF4 nanocrystals

Transparent, chloroform dispersed α-NaYF₄ nanocrystals doped with neodymium ions were synthesized and characterized. XRD and TEM measurement confirmed cubic structure of α-NaYF₄ of the nanoparticles (NPs). The absorption and emission spectra as well as ⁴F_3/2 level fluorescence decay curves were measured in order to estimate the influence of Nd³⁺ concentration in the matrix on the optical properties of the NPs. With the increase of Nd³⁺ doping level, the Judd-Ofelt Ω₄ parameter as well as the spectroscopic Nd³⁺ parameter X_Nd = Ω₄/Ω₆ was growing. In the same time the Ω₂ and Ω₆ were decreasing. Theoretical luminescence lifetimes of the ⁴F_3/2 level equal to ∼300 μs were also calculated and compared with the experimental values to quantify the concentration quenching. Based on this comparison, quantum efficiency was found to vary systematically between ∼100% and 4% for Nd³⁺ content increasing from 2 up to 25%.     

Correlation Between 3-D Surface Topography and Different Deposition Times of Engineered Ni@a-C:H Thin Films

Silicon - This study is aimed at analyzing the surface micromorphology of amorphous hydrogenated carbon layers containing nickel nanoparticles (Ni-NPs@a-C:H) within their structure, which were...     

Two-fold emission from the S-shell of PbSe/CdSe core/shell quantum dots

The optical properties of PbSe/CdSe core/shell quantum dots with core sizes smaller than 4 nm in the 5-300 K range are reported. The photoluminescence spectra show two peaks, which become increasingly separated in energy as the core diameter is reduced below 4 nm. It is shown that these peaks are due to intrinsic exciton transitions in each quantum dot, rather than emission from different quantum dot sub-ensembles. Most likely, the energy separation between the peaks is due to inter-valley coupling between the L-points of PbSe. The temperature dependence of the relative intensities of the peaks implies that the two emitting states are not in thermal equilibrium and that dark exciton states must play an important role.