Циклические нуклеотиды и патология печени

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“, Spitalul Clinic Republican, Conferința naţională de gastroenterologie şi hepatologie cu participare internaţională ”Actualităţi în gastroenterologie şi hepatologie” 16 iunie 2016 Chișinău, Republica MoldovaCyclic nucleotides (CN) cAMP and cGMP are recognized as cell signaling molecules that control a variety of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling and muscle relaxation. The alterations of CN signals were being observed in a number of pathophysiologic conditions, including liver disorders. In the liver, cAMP is distributed along the sinusoids and cGMP – in the nuclear elements and membranes of the hepatocytes. Their role is to mobilize the reserves of glucose and fatty acids from peripheral tissues. Alterations in the intracellular signaling process by cAMP has been shown to be involved in the pathological changes in colangiocyte: cholestatic secretory disorders and disorders associated with changes in cell proliferation, hepatocyte: advanced fi brotic processes as cirrhosis (CH), hepatocellular carcinoma (HCC). Cyclic AMP and cGMP can exert a stimulatory or inhibitory effect on cell proliferation depending on the cell type. This would suggest that disruption of intracellular signaling plays an important role in carcinogenesis. In patients with primary HCC were determined high serum levels of cAMP and cGMP. This data show the importance of studying CN as a potential cornerstone in the treatment of fibrotic processes and oncological pathologies, given the growing prevalence of this diseases worldwide, including in Moldova which leads after CH mortality index of the 192 Циклические нуклеотиды (ЦНК) цАМФ и цГМФ известны, как молекулы участвующие в передачи сигнала в клетке, которые регулируют множество биологических процессов, такие как адгезия и рост клеток, энергетический гомеостаз, передача нервного импульса, мышечное расслабление. Изменение сигналов ЦНК наблюдается в ряде патофизиологических процессов, в том числе и при патологии печени. В печени цАМФ распределен вдоль синусоидов, а цГМФ располагается в ядерных элементах и на плазматических мембранах гепатоцитов. Их роль заключается в мобилизации запасов глюкозы и жирных кислот из периферических тканей. Нарушения в процессе внутриклеточной передачи сигналов при участии цАМФ были доказаны при холестазе, холангитах и в других патологиях, связанных с изменением клеточного обмена на уровне гепатоцитов. Выраженные фиброзные изменения у больных с циррозом печени (ЦП), гепатоцеллюлярной карциномой (ГЦК). Изменяют уровень цАМФ и цГМФ, потом оказывают стимулирующее или ингибирующее действие на пролиферацию клеток в зависимости от их типа. Это позволяет предположить, что нарушение внутриклеточной передачи сигнала цАМФ и цГМФ играет важную роль при возникновении различных печеночных нарушений. При первичной ГЦК в сыворотке крови были выявлены высокие уровни цАМФ и цГМФ. Возможно нормализавания уровня ЦНК может иметъ важную роль в лечении фиброза и рака печени, распространенность которых возрастает во всем мире, в том числе и в Республике Молдова

Biological performances of plasmonic biohybrids based on phyto-silver/silver chloride nanoparticles

Silver/silver chloride nanoparticles (Ag/AgClNPs), with a mean size of 48.2 ± 9.5 nm and a zeta potential value of −31.1 ± 1.9 mV, obtained by the Green Chemistry approach from a mixture of nettle and grape extracts, were used as “building blocks” for the “green” development of plas-monic biohybrids containing biomimetic membranes and chitosan. The mechanism of biohybrid formation was elucidated by optical analyses (UV–vis absorption and emission fluorescence, FTIR, XRD, and SAXS) and microscopic techniques (AFM and SEM). The aforementioned novel materials showed a free radical scavenging capacity of 75% and excellent antimicrobial properties against Escherichia coli (IGZ = 45 mm) and Staphylococcus aureus (IGZ = 35 mm). The antiproliferative activity of biohybrids was highlighted by a therapeutic index value of 1.30 for HT-29 cancer cells and 1.77 for HepG2 cancer cells. At concentrations below 102.2 µM, these materials are not hemolytic, so they will not be harmful when found in the bloodstream. In conclusion, hybrid systems based on phyto-Ag/AgClNPs, artificial cell membranes, and chitosan can be considered potential adjuvants in liver and colorectal cancer treatment

Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)2Cl2] (1), [Zn(mptp)Cl2(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu2(dmtp)4Cl4]·2H2O (3) and [Zn(dmtp)2Cl2] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P21/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through π–π interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H∙∙∙π interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide