On h-convexity

We introduce a class of h-convex functions which generalize convex, s-convex, Godunova-Levin functions and P-functions. Namely, the h-convex function is defined as a non-negative function which satisfies f(αx+(1−α)y)?h(α)f(x)+h(1−α)f(y), where h is a non-negative function, α∈(0,1) and x,y∈J. Some properties of h-convex functions are discussed. Also, the Schur-type inequality is given.     

Binding behavior of amino acid conjugates of indole-3-acetic acid to immobilized human serum albumin

The affinity of indole-3-acetic acid (IAA), indole-3-propionic acid, indole-3-butyric acid and 24 of their amino acid conjugates to immobilized human serum albumin, as expressed by the retention factor k (determined by HPLC), was dependent on (1) lipophilicity, (2) chirality and (3) functional groups in the amino acid moiety; in some cases conformation plays an additional role. Two lipophilicity-related parameters afforded quantitative correlations with k: retention on a C18 reversed-phase column (experimental approach) and the distance between the hydrophilic and hydrophobic poles of the molecules (in silico approach). Most compounds examined are possible metabolic precursors of IAA, an experimental tumor therapeutic.     

Simple fitting of energy-resolved reactive cross sections in threshold collision-induced dissociation (T-CID) experiments

An operationally much simpler method for the extraction of thermochemical data from energy-resolved collision-induced dissociation cross sections, which is specifically designed for ligand binding energy determinations by tandem mass spectrometry, is presented. Compared to previous methods available in the literature, the present method has three advantages: (i) A more realistic treatment of the electrostatic potential for the approach of the ion to the collision partner leads to a better, nonempirical threshold function, allowing fitting of the cross section over the entire energy range rather than just the onset. (ii) Treatment of the kinetic shift with a new model for the density-of-states function eliminates the need for explicit entry of frequencies for the starting ion or the transition state without loss of accuracy relative to direct state counts. (iii) Data fitting using Monte Carlo simulation and a genetic algorithm instead of the usual Marquardt-Levenburg least-squares routines not only produces an equivalent fit but also produces statistically relevant error bounds on the derived fit parameters. Although the method is conceived for medium-to-large organometallic complexes, the theory is general enough to be appropriate for a wide range of binding phenomena of a small molecule to a larger one observed in mass spectrometry.     

Seasonal Variability of Volatilome from Dictyota dichotoma

Dictyotaceae, the large family of brown algae with the genus Dictyota as the richest one among them, produce a significant number of secondary metabolites, like diterpenes. The aim of this study was to investigate the variations in the composition of the volatile organic compounds (VOCs) of the brown alga Dictyota dichotoma collected from the Adriatic Sea. For the first time, both seasonal changes and the impact of air drying were examined. Headspace solid-phase microextraction (HS-SPME) on two fibres with different polarities and hydrodistillation (HD), followed by gas chromatography and mass spectrometry (GC-MS) analysis, was performed on both fresh (FrDd) and air-dried (DrDd) D. dichotoma. The major compounds of HS-FrDd were pentadecane and oct-1-en-3-ol. The percentage of pentadecane in HS-DrDd was increased up to 7.8 times in comparison with HS-FrDd. Principal component analysis (PCA) identified differences between the variability of data among fresh and dried samples over months and clearly dissociated the fresh May samples from the others in the HS-SPME results. The most abundant group of VOCs in HD were terpenes, with diterpenes isopachydictyol A and cembra-4,7,11,15-tetraen-3-ol as the major compounds. Diterpene pachydictyol A was also found and among sesquiterpenes and gleenol was the most abundant. Based on the dominant compound analyses, the PCA showed distinct separation of the fresh and dried samples, indicating similarities between the samples and allowing the establishment of typical VOCs significant for the chemotaxonomy of D. dichotoma.     

In Silico Screening of Natural Compounds for Candidates 5HT6 Receptor Antagonists against Alzheimer’s Disease

Alzheimer’s disease (AD), a devastating neurodegenerative disease, is the focus of pharmacological research. One of the targets that attract the most attention for the potential therapy of AD is the serotonin 5HT6 receptor, which is the receptor situated exclusively in CNS on glutamatergic and GABAergic neurons. The neurochemical impact of this receptor supports the hypothesis about its role in cognitive, learning, and memory systems, which are of critical importance for AD. Natural products are a promising source of novel bioactive compounds with potential therapeutic potential as a 5HT6 receptor antagonist in the treatment of AD dementia. The ZINC—natural product database was in silico screened in order to find the candidate antagonists of 5-HT6 receptor against AD. A virtual screening protocol that includes both short-and long-range interactions between interacting molecules was employed. First, the EIIP/AQVN filter was applied for in silico screening of the ZINC database followed by 3D QSAR and molecular docking. Ten best candidate compounds were selected from the ZINC Natural Product database as potential 5HT6 Receptor antagonists and were proposed for further evaluation. The best candidate was evaluated by molecular dynamics simulations and free energy calculations.     

Synthesis,Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC₅₀ values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditis elegans at concentrations up to 50 µg/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br_2, respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski’s “rule of five”, with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.     

Bis(phenylethynyl)arene Linkers in Tetracationic Bis-triarylborane Chromophores Control Fluorimetric and Raman Sensing of Various DNAs and RNAs

We report four new luminescent tetracationic bis-triarylborane DNA and RNA sensors that show high binding affinities, in several cases even in the nanomolar range. Three of the compounds contain substituted, highly emissive and structurally flexible bis(2,6-dimethylphenyl-4-ethynyl)arene linkers ( 3 : arene=5,5′-2,2′-bithiophene; 4 : arene=1,4-benzene; 5 : arene=9,10-anthracene) between the two boryl moieties and serve as efficient dual Raman and fluorescence chromophores. The shorter analogue 6 employs 9,10-anthracene as the linker and demonstrates the importance of an adequate linker length with a certain level of flexibility by exhibiting generally lower binding affinities than 3 – 5 . Pronounced aggregation–deaggregation processes are observed in fluorimetric titration experiments with DNA for compounds 3 and 5 . Molecular modelling of complexes of 5 with AT-DNA, suggest the minor groove as the dominant binding site for monomeric 5 , but demonstrate that dimers of 5 can also be accommodated. Strong SERS responses for 3 – 5 versus a very weak response for 6 , particularly the strong signals from anthracene itself observed for 5 but not for 6 , demonstrate the importance of triple bonds for strong Raman activity in molecules of this compound class. The energy of the characteristic stretching vibration of the C≡C bonds is significantly dependent on the aromatic moiety between the triple bonds. The insertion of aromatic moieties between two C≡C bonds thus offers an alternative design for dual Raman and fluorescence chromophores, applicable in multiplex biological Raman imaging.     

A Quadrupolar Bis-Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA,RNA and Proteins

A water-soluble tetracationic quadrupolar bis-triarylborane chromophore showed strong binding to ds-DNA, ds-RNA, ss-RNA, as well as to the naturally most abundant protein, BSA. The novel dye can distinguish between DNA/RNA and BSA by fluorescence emission separated by Δ =3600 cm⁻¹, allowing for the simultaneous quantification of DNA/RNA and protein (BSA) in a mixture. The applicability of such fluorimetric differentiation in vitro was demonstrated, strongly supporting a protein-like target as a dominant binding site of 1 in cells. Moreover, our dye also bound strongly to ss-RNA, with the unusual rod-like structure of the dye, decorated by four positive charges at its termini and having a hydrophobic core, acting as a spindle for wrapping A, C and U ss-RNAs, but not poly G, the latter preserving its secondary structure. To the best of our knowledge, such unmatched, multifaceted binding activity of a small molecule toward DNA, RNA, and proteins and the selectivity of its fluorimetric and chirooptic response makes the quadrupolar bis-triarylborane a novel chromophore/fluorophore moiety for biochemical applications.