Sinteza i kristalna struktura 1,2,3,4-tetrahidro-9-aminoakridin-tetrahlorocinkata(II) monohidrata

In the reaction of ZnCl(2) with tacrine hydrochloride in water novel tetracoordinated (C(13)H(15)N(2))(2)[ZnCl(4)]-H(2)O complex was obtained and characterized by elemental analysis, molar conductivity and X-ray analysis. The complex crystallizes in the space group P-1 of the triclinic crystal system. The structure contains two crystallographically different molecules of protonated tacrine present as counter cations, the [ZnCl(4)](2-) complex anion and one water solvent molecule. The counter cations slightly differ in the puckering of the cyclohexene ring. The molecules of protonated tacrine are involved in different intermolecular hydrogen bonds. In the crystal, the hydrogen bonding generates a 3D assembly. In the crystal, pi center dot center dot center dot pi stacking interactions between the rings of protonated tacrine were evidenced. The [ZnCl(4)](2-) complex anion has a distorted tetrahedral geometry. Three out of the four Cl atoms are involved in intermolecular hydrogen bonding. The intermolecular H-bond interactions involving the Cl atoms affect the Zn-CI bond lengths.U reakciji ZnCl2 sa takrin-hidrohloridom u vodi, dobijen je novi tetrakoordinovani (C13H15N2)2[ZnCl4]?H2O kompleks koji je okarakterisan pomoću elementalne analize, molarne provodljivosti i rendgenske strukturne analize. Kompleks kristališe u prostornoj grupi P?1 trikliničnog kristalnog sistema. Struktura sadrži dva kristalografski različita molekula protonovanog takrina koji su prisutni kao kontra-katjoni, [ZnCl4]2 kompleksni anjon i molekul kristalne vode. Molekuli katjona se neznatno razlikuju u stepenu nabiranja cikloheksenovog prstena. Molekuli protonovanog takrina su uključeni u različite intermolekulske vodonične veze. Intermolekulsko vodonično vezivanje u kristalu generiše 3D molekulski skup pi...pi interakcije između prstenova protonovanog takrina su primećene u kristalu. [ZnCl4]2- ima distorgovanu tetraedarsku geometriju. Tri od četiri Cl atoma su uključena u intermolekulske vodonične veze. Intermolekulske vodonične interakcije koje uključuju Cl atome utiču na dužinu Zn-Cl veza

Produkcija H2O2 i NO peritonealnih makrofaga pacova u odgovoru na crevne komensalne bakterije

The importance of commensal bacteria in the immune system development and its involvement in the etiopatogenetic mechanisms of complex multifactorial and multigenic diseases is well documented. The aim of the present study was to compare the levels of hydrogen peroxide (H2O2) and nitric oxide (NO) produced by resident peritoneal macrophages from the autoimmune disease susceptible Dark Agouti (DA) rats vs. resistant Albino Oxford (AO) rat strain, under basal conditions and subsequent to in vitro stimulation with gut commensals. Following the stimulation with phorbol myristil acetate (PMA), E. coli/PMA or P. mirabilis/PMA, AO rats macrophages have produced significantly higher levels of H2O2 compared to the cells from DA rats. Strain differences in NO production were not detected under basal conditions and after the stimulation with lipopolysaccharide and P. mirabilis. However, after the in vitro stimulation with E. coli, AO rats macrophages have produced higher levels of NO compared to DA rats macrophages. Our results demonstrated that macrophages from AO rats have higher potential to produce H2O2 and NO in response to specific commensal bacteria when compared to DA rats. A possible relationship between the macrophage activity in response to commensal bacteria and the susceptibility to induction of autoimmune/inflammatory diseases in AO and DA rat strains is suggested.Poznato je da komensalna crevna flora ima značajnu ulogu u razvoju imunskog sistema kao i u etiopatogenezi kompleksnih multifaktorijalnih i multigenetskih bolesti. Cilj ovog rada bio je da se uporedi produkcija vodonik peroksida (H2O2) i azot monoksida (NO) peritonealnih makrofaga dva inbredna soja pacova, od kojih je jedan osetljiv (Dark Agouti, DA), a drugi rezistentan (Albino Oxford, AO) na indukciju autoimunskih bolesti, kako u bazalnim uslovima tako i nakon in vitro stimulacije makrofaga sa crevnim komensalima. Nakon stimulacije sa forbol miristil acetatom (PMA), E. coli/PMA and P. mirabilis/PMA makrofage AO pacova su produkovale značajno više H2O2 u poređenju sa makrofagama DA pacova. Nisu detektovane sojne razlike u produkciji NO u bazalnim uslovima, kao ni posle stimulacije sa lipopolisaharidom i P. mirabilis. Međutim, nakon in vitro stimulacije sa E. coli makrofage AO pacova su produkovale više NO u odnosu na makrofage DA pacova. Naši rezultati su ukazali da makrofage AO pacova imaju veći potencijal za produkciju H2O2 i NO u odgovoru na specifične komensalne bakterije. Ova različita aktivnost makrofaga može biti u vezi sa različitom osetljivošću na indukciju autoimunskih/inflamatornih bolesti kod DA i AO soja pacova

Acid–base equilibria of the Zn(II) and Fe(III) complexes with condensation products of 2-acetylpyridine and the dihydrazide of oxalic and malonic acid

Acid–base equilibria of Zn(II) and Fe(III) complexes with N',N'2-bis[(1E)-1-(2-pyridyl)ethylidene]ethanedihydrazide (ligand L1) and N',N'2-bis[(1E)-1-(2-pyridyl)ethylidene]propanedihydrazide (ligand L2), i.e., [Fe(L1)Cl2(H2O)], [Fe(L2)Cl(H2O)]2+, [Zn(L1)(H2O)3]+ and [Zn(L2)(H2O)2]2+, which expressed cytotoxic activity, were investigated in aqueous media. The equilibrium constants were determined potentiometrically at 25 °C at a constant ionic strength of 0.10 mol/dm3 (Na2SO4). The results showed that at pH < 8 both the Fe(III) complexes studied here have three, while [Zn(L1)(H2O)3]+ and [Zn(L2)(H2O)2]2+ have one and two titratable protons, respectively. Based on the obtained values for the equilibrium constants, protonation schemes of the examined complexes are proposed

Visoki antioksidativni potencijal i mali toksični efekat selenosemikarbazonskih kompleksa

Novel metal-based compounds with therapeutic potential have become the subject of intense investigations in inorganic chemistry and biomedical science. Recently, strong dose-dependent cytotoxic activities of selenosemicarbazone metal complexes against several human cancer cell lines were demonstrated. The aim of the present study was to investigate in vitro antioxidative potential of Ni(II), Cd(II) and Zn(II) selenosemicarbazone complexes. All three investigated complexes exhibited high 2,2'-azinobis(3-ethyl-benzothiazoline-6-sulphonic acid) radical cation (ABTS(center dot+)) scavenging capacity, comparable with ascorbic acid. In an acute toxicity study, administration of the compounds was performed orally to mice at single doses. The mice were observed for clinical signs, body weight effects and mortality for 14 days, after which they were sacrificed for gross organ necropsy. The body weight did not vary after administration, and the autoptic analysis failed to show appreciable macroscopic alterations of internal organs. Generally, the compounds exhibited low toxic effects as required for further in vivo therapeutic studies.Nova jedinjenja na bazi metala sa terapeutskim dejstvom postala su predmet istraživanja u neorganskoj hemiji i biomedicinskim naukama. Pokazana je jaka dozno-zavisna citotoksična aktivnost kompleksa selenosemikarbazona na većem broju ćelijskih linija humanih ćelija kancera. Cilj rada je ispitivanje in vitro antioksidativnog dejstva selenosemikarbazonskih kompleksa nikla, cinka i kadmijuma. Sva tri ispitivana kompleksa pokazala su jaku antioksidativnu aktivnost prema ABTS radikalu, uporedivu sa aktivnošću askorbinske kiseline. Tokom ispitivanja akutne toksičnosti, jedinjenja su oralno davana miševima u pojedinačnim dozama i praćeni su klinički znaci, težina tela i mortalitet nakon 14 dana, a potom su životinje žrtvovane radi autopsije organa. Težina tela nije varirala nakon aplikacije. Generalno, jedinjenja su pokazala mali toksični efekat što i zahteva buduće in vivo terapeutsko ispitivanje

Karakterizacija Intor:Swiss soja albino miševa donetog u Institut za virusologiju, vakcine i serume - Torlak početkom XX veka

The Institute of Virology, Vaccines and Sera Torlak was established in 1927, while the first vaccine was produced in the Institute in 1930. Vaccines production implies using experimental animals, including mice, in in-process controls. The laboratory mice which have been in use in Torlak Institute from the very beginning belong to Swiss albino outbred stock. This stock, which has been in use for more than 80 years contains a large number of mice maintained at all times, was recently named Intor:Swiss. Biological characteristics of Intor:Swiss stock, are presented in this paper for the first time. Taking into account the presented characteristics, the Institute Torlak's Swiss mice are suitable for use in pharmaceutical studies, vaccine development research and basic research, as well as in toxicological studies. The publication of data on the Intor:Swiss mice represents a contribution to the international scientific community, since it offers the possibility for obtaining an additional outbred mouse stock for research.Institut za Virusologiju, vakcine i serume Torlak, osnovan je 1927., a prva vakcina u Institutu proizvedena je 1930. Proizvodnja vakcina je složen proces koji između ostalog podrazumeva i korišćenje eksperimentalnih životinja u kontroli samog procesa. Laboratorijski miševi koji su od samog početka bili u upotrebi u Institutu Torlak, pripadaju Swiss albino outbred soju. Ova kolonija je u upotrebi više od 80 godina i sve vreme se sastoji od velikog broja jedinki što omogućava očuvanje genetske raznolikosti, pa samim tim i outbred karakteristika. Ovi miševi su odnedavno registrovani pod imenom Intor:Swiss, i njihove biološke osobine su u ovom radu prikazane po prvi put. Swiss miševi Instituta Torlak pogodni su za upotrebu u farmaceutskim studijama, za razvojno istraživanje vakcina, osnovna istraživanja i toksikološka ispitivanja. Zbog svega navedenog Intor:Swiss miševi predstavljaju još jedan pogodan animalni model za ispitivanje lekova i vakcina

Strain differences and the role for HSP47 and HSP70 in adjuvant arthritis in rats

Because of high sequence homology between microbial and endogenous heat shock proteins (HSP), immunological cross-reactivity to microbial HSP has been suggested as a possible cause of the development of autoimmune diseases, such as rheumatoid arthritis. The present study aimed to determine a potential role of HSP47, a molecular chaperone involved in the synthesis and assembly of collagen molecules, and microbial HSP71 (mHSP71) in adjuvant arthritis (AA) in two rat strains: Dark Agouti (DA), susceptible to AA induction and Albino Oxford (AO), which is resistant to AA induction. Immunization with complete Freund's adjuvant (CFA) induced an increased expression of HSP47 in joints of DA rats, which exhibited severe clinical signs of AA at the time of disease peak, while this protein was not detectable in joints of AO rats. In contrast, no strain differences in HSP72 (rat analogue of mHSP71) expressions in joints were observed. The increased levels of anti-HSP47 antibodies were detected in sera of DA rats during the AA peak, while the immunization with CFA increased levels of anti-mHSP71 antibodies in sera of AO rats. HSP47 and mHSP71 reduced proliferation of draining inguinal lymph node cells (LNC) in resistant AO rat strain, leading to a hypothesis that both HSP participated in AA control. Finally, mHSP71 potentiated the apoptotic response of LNC in susceptible DA rat strain. In conclusion, our findings indicate involvement of HSP47 in the development of AA in the rat, and point out to the regulatory role for both HSP47 and mHSP71

2,2 '-{1,1 '-[2,2 '-Oxalylbis(hydrazin-2-yl-1-ylidene)]diethylidyne}dipyridinium bis(perchlorate) dihydrate

The title salt, C(16)H(18)N(6)O(2)(2+)center dot 2ClO(4)(-)center dot 2H(2)O, was obtained unintentionally as a major product in the reaction of Zn(ClO(4))(2)center dot 6H(2)O with the N',N'(2)-bis[(1E)-1-(2-pyridyl)ethylidene]ethanedihydrazide (H(2)L) ligand. The (H(4)L)(2+) cation lies across a centre of inversion. The pyridiniumimine fragments of (H(4)L)(2+) adopt syn orientations. Intramolecular N-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds lead to the formation of S(5) motifs. In the crystal, neighbouring cations are connected by pi-pi interactions between pyridinium units with a centroid-centroid distance of 3.600 (1) angstrom. Moreover, the crystal components are assembled into two-dimensional layers via N-H center dot center dot center dot O and O-H center dot center dot center dot O hydrogen bonds, with no direct hydrogen-bonding interactions between cations

Fenotipske promene izazvane imunizacijom encefalitogenom menjaju funkcije peritonealnih makrofaga u dva soja pacova različite osetljivosti prema indukciji eksperimentalnog autoimunskog encefalomijelitisa (EAE).

We have investigated the phenotype of peritoneal cells and the functions of peritoneal macrophages obtained from experimental autoimmune encephalomyelitis (EAE)-susceptible Dark Agouti (DA) and EAE-resistant Albino Oxford (AO) rat strains on days 1, 3 and 7 post immunization with encephalitogen. Resident peritoneal cells from immunized and non-immunized rats of both strains were subjected to flow cytometric analyzes and after adherence were tested for zymosan phagocytosis, hydrogen peroxide (H2O2) and nitric oxide (NO) production. In non-immunized rats, macrophages from the DA rat strain phagocytosed more zymosan but produced less H2O2 than cells from the AO strain, while both strains produced comparable amounts of NO. Immunization increased phagocytosis in DA rats' cells, but decreased both phagocytosis and H2O2 production in cells from AO rats. Overall higher phagocyte ability in DA rats was associated with a significantly larger population of ED1+ cells (macrophages and dendritic cells), in contrast to a more pronounced expression of ED2 antigen (resident macrophages) on cells from AO rats. Immunization also increased the expression of CD11b molecule on non-resident ED2-macrophages of DA, but not of AO rats. The early and subtle phenotype changes in peritoneal cells of both rat strains might mirror the mechanism contributing to their different sensitivity to the induction of autoimmunity.Ispitivan je fenotip peritonealnih ćelija, kao i funkcije peritonealnih makrofaga, izolovanih od pacova Dark Agouti (DA) soja osetljivog na indukciju eksperimentalnog autoimunskog encefalomijelitisa (EAE) i pacova Albino Oxford (AO) soja koji je rezistentan prema EAE-u, 1, 3. i 7. dana nakon imunizacije encefalitogenom. Rezidentne peritonealne ćelije su ispitivane metodom protočne citofluorometrije, a zatim je nakon adherence testirana njihova sposobnost fagocitoze čestica zimozana i kapacitet produkcije vodonik peroksida (H2O2) i azot monoksida (NO). U neimunizovanih pacova makrofage DA soja su intenzivnije fagocitovale čestice zimozana i imale nižu sposobnost produkcije H2O2 nego ćelije pacova AO soja, ali nije bilo sojnih razlika u sposobnosti produkcije NO. Imunizacija je dovela do povećanja fagocitne sposobnosti makrofaga DA pacova, ali i do smanjenja fagocitoze i produkcije H2O2 makrofaga pacova AO soja. Generalno veću sposobnost fagocitoze u DA pacova prati i značajno veća zastupljenost ED1+ ćelija (koje čine uglavnom makrofage i dendritične ćelije) nasuprot većoj zastupljenosti ED2 antigena (marker rezidentnih makrofaga) na ćelijama pacova AO soja. Imunizacija encefalitogenom je takođe dovela do povećanja ekspresije CD11b molekula na nerezidentnim ED2- ćelijama pacova DA, ali ne i AO soja. Rane i diskretne fenotipske promene na peritonealnim ćelijama pacova oba soja verovatno odslikavaju mehanizme koji doprinose njhovoj različitoj osetljivosti prema indukciji autoimunskih oboljenja

Razlike u edemu šape pacova indukovanom konkanavalinom a u zavisnosti od soja - uticaj histaminskih H1 i H2 receptora

The present study tests the hypothesis that the difference in the intensity of paw edema found between the Dark Agouti (DA) and Albino Oxford (AO) rat strains originates from the distinct participation of histamine, serotonin and their corresponding receptors in Concanavalin A (Con A)-induced inflammation. DA and AO male rats were intraplantarly injected with specific receptor antagonists prior to Con A, and the intensity of inflammation was determined by measuring the paw diameter. Our results have showed that histamine H1 and H2 receptor antagonists reduced the Con A-induced paw edema in DA rats, while serotonin 5HT3 receptor antagonist diminished the inflammation in both DA and AO rat strains. The calcium channel blocker did not change Con A-induced inflammation. Strain differences in the intensity and kinetics of inflammation observed between the DA and AO rats are most likely defined by the diversity of mediators released and their receptors activated upon Con A injection.Testirana je hipoteza da razlike u intenzitetu inflamatornog edema šape indukovanog konkanavalinom A u pacova Dark Agouti (DA) i Albino Oxford (AO) soja potiču od različitog doprinosa histamina i serotonina i njihovih odgovarajućih receptora. Mužjaci pacova DA i AO soja su intraplantarno tretirani antagonistima specifičnih receptora pre izazivanja inflamacije konkanavalinom A i intenzitet inflamacije je praćen merenjem dijametra šape. Naši rezultati su ukazali da antagonisti histaminskih H1 i H2 receptora smanjuju edem šape indukovan konkanavalinom A u DA pacova, dok antagonist serotoninskih 5HT3 receptora smanjuje edem šape u oba soja pacova. Blokator kalcijumskih kanala ne utiče na inflamaciju izazvanu konkanavalinom A. Razlike u intenzitetu i kinetici inflamatornog odgovora indukovanog konkanavalinom A između DA i AO sojeva su najverovatnije posledica razlika u oslobođ enim medijatorima i aktivaciji odgovarajućih receptora nakon injekcije konkanavalina A

Synthesis of a New Family of Zn(II) Hydrazone Complexes: Characterisation, Catalytic Activity, and DFT Calculations

The ligand (E)-2-(1-(thiazol-2-yl)ethylidene)hydrazine-1-carbothioamide (HL1 ) was obtained from the condensation of 2-acetylthiazole and thiosemicarbazide. Upon reacting HL1 with Zn(BF4)2·6H2O and NaN3 in a solvent mixture of water/methanol, mononuclear Zn(II) complex 1 with the composition [ZnL1 (N3)2] was obtained. In complex 1, Zn(II) is pentacoordinated with the thiazole nitrogen, the azomethine nitrogen, and thiolate sulfur atoms from the deprotonated hydrazone ligand, as well as with two azido ligands. Complex 1 crystallises in the monoclinic crystal system with space group No.14 (P21/c cell setting). The unit cell of 1 contains four [ZnL1 (N3)] asymmetric units. In complex 1, the Zn(II) site shows a distorted geometry, almost midway between the square pyramid and trigonal bipyramid, established on the basis of a calculated τ5 parameter of 0.46. The hydrazone ligand (E)-1-(2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethyl)-pyridine1-ium chloride (HL2 Cl) was obtained from the condensation reaction of 2-acetylpyridine and Girard's P reagent. Reaction of HL2 Cl with Zn(BF4)2·6H2O and NaN3, in a mixture of acetonitrile/water/methanol, gives mononuclear Zn(II) complex 2 with the composition [ZnL2 (N3)2]. Reaction of HL2 Cl with Zn(BF4)2·6H2O and NaN3, in a mixture of acetonitrile/water/methanol, gives mononuclear Zn(II) complex 2 with the composition [ZnL2 (N3)2]. In complex 2, the Zn(II) ion has fivefold coordination with NNO-set of donor atoms of L2 and two nitrogen atoms from the azido ligands. The calculated τ5 value of 0.08 for [ZnL2 (N3)2] indicates that the five-coordination geometry of the Zn(II) ion is slightly distorted square pyramidal. Evaluation of the catalytic properties of the Zn(II) complexes in the KA2 reaction shows that the most active compound, when used as a catalyst, is complex 1. It leads to a 92 % isolated yield of the desired propargylamine product. The catalytic activity results are in full agreement with the findings of the DFT calculations. Complex 1 shows the highest value of molecular softness and the lowest value of molecular hardness. This correlation, between experimental and theoretical results, is excellently visualised in the linear relationship between the isolated yield of the desired propargylamine product and the calculated molecular softness, S.Poster: [https://cer.ihtm.bg.ac.rs/handle/123456789/7318