Proline-rich polypeptides (Colostrinin®/COLOCO®) modulate BDNF concentration in blood affecting cognitive function in adults: A double-blind randomized placebo-controlled study.

Proline-rich polypeptides (PRPs complex also known as COLOCO®, Colostrinin®) consist of low-molecular weight peptides ranging up to 10 kDa, isolated from the bovine colostrum obtained up to 48 h postpartum. PRPs have been shown to affect processes involved in inflammation, brain aging, and neurodegeneration. The aim of this study was to investigate the effect of Colostrinin® (COLOCO®) on the cognitive abilities of healthy volunteers in three different age groups using the CANTAB tool in a double-blind randomized placebo-controlled study. BDNF serum level was used as a physicochemical marker of improvement of the cognitive skills. Three hundred and sixty-one healthy volunteers were divided into three study groups aged 18-24, 25-54, and 55-75; each group was then divided into two subgroups which took either placebo or tested lozenge with 120 µg of PRPs for the period of 4 months. The CANTAB battery test was used to measure the efficacy of PRP in the context of cognitive functioning. After the treatment with COLOCO®, we observed differences within MoCA score in the oldest patients, improvement in DMS and drop in PAL scores within the youngest group, drop in RTI and improvement in RVP scores within the middle-aged group. It was observed that serum BDNF level increased in all study groups which confirms cognitive improvement. In conclusion, we have shown that Colostrinin® exhibits cognitive enhancing effects, probably through the modulation of BDNF concentrations.

Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives.

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.

The Cytotoxic Effect of Copper (II) Complexes with Halogenated 1,3-Disubstituted Arylthioureas on Cancer and Bacterial Cells.

A series of eight copper (II) complexes with 3-(4-chloro-3-nitrophenyl)thiourea were designed and synthesized. The cytotoxic activity of all compounds was assessed in three human cancer cell lines (SW480, SW620, PC3) and human normal keratinocytes (HaCaT). The complexes 1, 3, 5, 7 and 8 were cytotoxic to the studied tumor cells in the low micromolar range, without affecting the normal cells. The complexes 1, 3, 7 and 8 induced lactate dehydrogenase (LDH) release in all cancer cell lines, but not in the HaCaT cells. They provoked early apoptosis in pathological cells, especially in SW480 and PC3 cells. The ability of compounds 1, 3, 7 and 8 to diminish interleukin-6 (IL-6) concentration in a cell was established. For the first time, the influence of the most promising Cu (II) complexes on intensities of detoxifying and reactive oxygen species (ROS) scavenging the enzymes of tumor cells was studied. The cytotoxic effect of all copper (II) conjugates against standard and hospital bacterial strains was also proved.