Structure-activity relationship and cytotoxicity of the new thiosemicarbazide derivatives and their Cu(II) complexes against prostate and melanoma cancer cells.

In this study, eighteen new ligands (B1-B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl2, Cu(B4)Cl2, Cu(B10)Cl2, Cu(B17)Cl2, Cu(B18)Cl2). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1-B18 compounds, B3, B5, B9, B10, B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl2 reaching the IC50 value equal to 88 µM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety.

Association Analysis of Polymorphic Variants of the BDNF Gene in Athletes.

As BDNF is one of the group of neurotrophins highly influencing the processes happening in the brain, such as the processes of learning and personality creation, we decided to look closer at its genetic variations in association with the personality of a group of athletes and their controls. The study group consisted of 305 volunteers: martial arts athletes (n = 153; mean age = 24.06) and healthy non-athletes as controls (n = 152; mean age = 22.23). Thirty-eight percent of the martial arts group achieved the championship level. Both the martial arts and control subjects were examined using the NEO Five-Factor Personality Inventory (NEO-FFI) and the State-Trait Anxiety Inventory (STAI) scales. The results of the NEO-FFI and STAI inventories were given as sten scores. The conversion of the raw score to the sten scale was performed according to Polish norms for adults. Genomic DNA was extracted from blood leukocytes and then genotyped using a PCR method for the following polymorphisms: BDNF rs10767664 and BDNF rs2030323. We observed statistical significance for both polymorphisms when comparing martial arts athletes with the control group in relation to the conscientiousness and extraversion scales. However, since few extant articles consider this association, our results still require further analysis, probably by considering a larger group.

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells.

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies.

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 µg/mL), Mycobaterium pheli (MIC = 7.81 µg/mL) and Mycobacerium timereck (62.6 µg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25-62.5 µg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity.

Synthesis, Spectral, Thermal and Biological Studies of 4-Cyclohexyl-3-(4-nitrophenyl)methyl-1,2,4-triazolin-5-thione and Its Copper(II) Coordination Compound, [CuCl2(H2O)2L2].

One of the strategies for seeking new biologically active substances is to modify compounds with potential biological activity. In this paper, 1,2,4-triazolin-5-thione derivative (3) was obtained in the cyclization reaction of appropriate thiosemicarbazide (2) as an organic ligand. The copper(II) complex, [CuCl2(H2O)2L2] (L=4-cyclohexyl-3-(nitrophenyl)methyl-1,2,4-triazolin-5-thione) (Cu-3) was prepared in a reaction of free ligand (3) with a CuCl2·2H2O solution in MeOH/EtOH mixture at room temperature. TGA data show that Cu-3 and free ligand are stable at room temperature. Both compounds were screened in vitro for antibacterial and antifungal activities using the broth microdilution method. The obtained complex (Cu-3) showed higher antibacterial effect, especially towards Gram-positive bacteria (with moderate activity and Minimal Inhibitory Concentration MIC = 250-500 µg/mL) than the free ligand (3) (with mild or no bioactivity and MIC ≥ 1000 µg/mL). In turn, yeasts, belonging to Candida albicans, exhibited similar sensitivity to both the copper(II) complex (Cu-3) and the organic ligand (3). The anticandidal activity of these compounds was moderate (MIC = 500 µg/mL), or, in the case of other Candida spp., lower (MIC ≥ 1000 µg/mL).

Chemical stability of fructans in apple beverages and their influence on chronic constipation.

The aim of this study was to analyse the concentration of reducing sugars in beverages based on apple juice with the addition of 2 and 4% of native and high polymerized inulin as well as oligofructose. Moreover, the effect of the consumption of this potentially prebiotic beverage containing highly polymerized inulin (12 g per 300 mL) on constipation was analysed. Pasteurization of the studied beverages followed by 120-day storage at ambient temperature, carried out in three independent trials, did not cause the hydrolysis of fructans into reducing sugars. Sensory analysis showed that the presence of fructans in beverages based on apple juice did not change the colour, clarity, odour, flavour, sweetness and acidity in comparison to apple juice. A placebo-controlled, randomized study involving 20 volunteers of age 20-29 with symptoms related to chronic constipation showed that the consumption of juice enriched with highly polymerized inulin significantly (p≤ 0.05) increased the frequency of bowel movements and facilitated defecation. The final conclusion is that fructans in beverages based on apple juice are chemically stable, do not affect sensory sensation and can help those with chronic constipation.

Deterioration of basic coordinative parameters defines life quality of elderly.

The objective of the studies was to analyze the level of deterioration of basic coordinative parameters and to derive the present correlation. 180 female participants with no neurological disorders and limb surgery were studied by means of flamingo, kinesthetic differentiation, spatial orientation and reaction to signals tests. t-test for un-paired data and Pearson correlation analyses were performed. Nonlinear gradual deterioration of studied parameters in function of age was observed. The correlation between postural balance, kinesthetic differentiation, and reaction to signals was observed. The obtained results indicate that significant correlation between the coordinative parameters may influence daily life functioning. It has also been shown that decline of the basic coordinative parameters can be driven be neurodegenerative processes and environmental factors such as high calorie intake, physical and mental inactivity, toxins and/or infectious agents.

Correlations between postural stability and strength of lower body extremities of women population living in long-term care facilities.

The present study was aimed at analyzing correlation between strength of lower body extremities and postural stability in function of age. A pool of 180 women divided into 6 age groups (65-69, 70-74, 75-79, 80-84, 85-89 and 90-94 years) was examined. They all were informed-consent participants. The results suggest that age is negatively correlated with lower body strength and positively correlated with decrease of postural balance. There is also an exponential correlation between the strength of lower body part and postural balance. The conclusion was derived that postural stability is at least partially controlled by the strength of lower body. The age of 75 in women population seems to be a threshold above which the neurodegenerative and muscle degeneration processes are responsible for significant increase of risk of fall.