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This article is a part of a scientific project focused on obtaining a new type of composite materials that are characterized by singlet oxygen generation upon irradiation with red light, which can be used as antibacterial agents. The composite material is nanoscale graphite oxide (GO) particles covalently bonded to an axially substituted zirconium phthalocyanine complex. For this purpose, two phthalocyanine zirconium complexes, axially mono-substituted with 4-aminosalicylic or 4-aminophthalic acids, were prepared and measured in terms of structure, morphology, and spectroscopic properties. The zirconium phthalocyanines are photosensitizers, and the axial ligands are bridging links connecting the complexes to the GO carrier (due to their terminal amino groups and carboxyl groups, respectively). The axial ligand in zirconium phthalocyanine complexes has a strong influence on the stability and optical properties of composite materials and, consequently, on reactive oxygen species (ROS) generation. In this paper, the effect of composite components (4-aminophthalato or 4-aminosalicylato substituted zirconium phthalocyanine complex as a photosensitizer and graphite oxide as a carrier and modulator of the action of active components) on ROS generation for potential antibacterial use is discussed.

BACKGROUND: A possible reduction in stocks of medicinal plant raw materials of Thymus serpyllum L. and Thymus vulgaris L. leads to the need to expand the raw material base of the official medicinal plants with using of endemic species of the flora of Kazakhstan, in particular, Thymus rasitatus Klokov, and Thymus eremita Klokov. AIM: The aim of the study was to study the possibility of using 70% ethanol extracts of T. rasitatus and T. eremita as antimicrobial agents. MATERIALS AND METHODS: The aerial parts of T. rasitatus and T. eremita were extracted with 70% ethanol using ultrasound assisted extraction. The qualitative and quantitative analyses of the 70% ethanol extracts were determined using the liquid chromatography-detection-ESI-mass spectrometry-(MS)/MS technique. The study of the antimicrobial activity of these extracts was performed for eight strains of Gram-positive bacteria, six strains of Gram-negative bacteria, and four cultures of fungi. RESULTS: Chromatographic analysis of hydroalcoholic extracts of both investigated Thymus species showed very similar phenolic compounds composition. In both cases, the major components are luteolin-7-O-glucoside and rosmarinic acid. About 70% ethanol extracts of T. rasitatus and T. eremita have a broad spectrum of antimicrobial activity, exhibit the bactericidal or bacteriostatic activity against all tested bacteria and fungi at concentration range of 0.0195–20 mg/ml, but differ in their potency against tested strains of microorganisms. CONCLUSION: About 70% ethanol extracts of T. rasitatus and T. eremita, endemic plants in the flora of Kazakhstan, can be considered as potential drugs with a wide spectrum of antimicrobial activity. The results of chromatographic analysis could be used for drug standardization.

BACKGROUND: The medicinal plant of Thymus serpyllum L. in nature, depending on the geographical region, climatic conditions, and growing environment, is represented with some chemotypes. Composition and quantitative content of the basic groups of the biologically active substances can be differed, and thus their biological properties are also various. AIM: The aim of the study was to determine possibility of the using the ultrasonic extracts of two chemotypes of T. serpyllum L. of Central Kazakhstan as an antimicrobial agent against test strains of microorganisms. MATERIALS AND METHODS: Two samples of T. serpyllum were extracted with 70% ethanol using ultrasound. The polyphenol content of the ultrasound extracts was determined using the LC-ultraviolet-ESI- tandem mass spectrometry technique. A study of an antimicrobial activity of the ultrasonic extracts was performed with eight strains of Gram-positive bacteria, six strains of Gram-negative bacteria, and four cultures of fungi. RESULTS: The ultrasonic extracts of two chemotypes of T. serpyllum L. are similar in composition of phenolic compounds but differ in a quantitative content of phenolic acids and flavonoids, except for a rosmarinic acid. The ultrasonic extracts have a wide spectrum of antimicrobial activity, exhibit the bactericidal or bacteriostatic activity against all tested bacteria and fungi at a concentration of 0.0625–20 mg/ml, but differ in their strength of action against test strains of microorganisms. CONCLUSION: The ultrasonic extracts of two chemotypes of T. serpyllum L. of Central Kazakhstan can be considered as a potential drug with a wide spectrum of antimicrobial activity. The results of chromatographic analysis will be used for standardization of a drug.

Four new picolinohydrazonamide derivatives, namely, 6-methyl-N′-(morpholine-4-carbonothioyl)picolinohydrazonamide, C12H17N5OS, 6-chloro-N′-(morpholine-4-carbonothioyl)picolinohydrazonamide methanol monosolvate, C11H14ClN5OS·CH3OH, 6-chloro-N′-(4-phenylpiperazine-1-carbonothioyl)picolinohydrazonamide, C17H19ClN6S, and 6-chloropicolinohydrazonamide, C6H7ClN4, have been synthesized and characterized by NMR spectroscopy and single-crystal low-temperature X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The first three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules in the structure. They also adopt the same symmetry, i.e. P21/c (P21/n), unlike the fourth structure which is chiral and has the space group P212121. For all the studied cases, intermolecular N—H...O and N—H...N hydrogen bonds play an essential role in the formation of the structures.

Two series of rhodanine-3-acetic and rhodanine-3-propionic acids derivatives having benzylidene and cinnamylidene substituents with additional electron donating and withdrawing groups at the C-5 position, were synthesised. The structures of the obtained derivatives were confirmed by spectroscopic methods and their lipophilicity was screened. The crystal structures were determined for selected compounds. The antibacterial activity of the derivatives was depended on the type of carboxyalkyl group in the N-3 position and on the type of the substituent in the C-5 position. The derivatives of rhodanine-3-propionic acid demonstrated the highest activity against Gram-positive bacteria. However, none of tested derivatives showed activity against Gram-negative bacteria and yeast. We believe that the presence of the N,N-diethylamine group in the aromatic system and the number of carbon atoms in the carboxyalkyl group is more significant for the biological activity than the fact that the benzylidene or cinnamylidene substituent was present at the C-5 position. Keywords: Rhodanine, Rhodanine-3-carboxyalkyl acids, Antibacterial activity, Antimicrobial activity, Thiazolidine-4-one

The oral cavity is inhabited by a wide spectrum of microbial species, and their colonization is mostly based on commensalism. These microbes are part of the normal oral flora, but there are also opportunistic species that can cause oral and systemic diseases. Although there is a strong exposure to various microorganisms, the oral mucosa reduces the colonization of microorganisms with high rotation and secretion of various types of cytokines and antimicrobial proteins such as defensins. In some circumstances, the imbalance between normal oral flora and pathogenic flora may lead to a change in the ratio of commensalism to parasitism. Healthy oral mucosa has many important functions. Thanks to its integrity, it is impermeable to most microorganisms and constitutes a mechanical barrier against their penetration into tissues. Our study aims to present the role and composition of the oral cavity microbiota as well as defense mechanisms within the oral mucosa which allow for maintaining a balance between such numerous species of microorganisms. We highlight the specific aspects of the oral mucosa protecting barrier and discuss up-to-date information on the immune cell system that ensures microbiota balance. This study presents the latest data on specific tissue stimuli in the regulation of the immune system with particular emphasis on the resistance of the gingival barrier. Despite advances in understanding the mechanisms regulating the balance on the microorganism/host axis, more research is still needed on how the combination of these diverse signals is involved in the regulation of immunity at the oral mucosa barrier.

A comprehensive approach to the mineral composition of black teas of different origins was studied using the Flame Atomic Absorption Spectrometry (FAAS) method, supported by chemometric tools including Principal Component Analysis PCA) and Classification and Regression Trees (CART). Significant differences between the teas from seven countries (Japan, Nepal, Kenya, Iran, Sri Lanka, India, and China) were shown. K was the main element determined in all teas, with an average concentration of 11,649 mg/kg, followed by Ca, Mg and Mn. In general, regarding all investigated black teas, the element content was ranked in the following order: K &gt, Ca &gt, Mg &gt, Mn &gt, Fe &gt, Na &gt, Zn &gt, Cu. The applied chemometric methods allowed us to recognize black tea clusters based on their mineral composition and place of cultivation, and allowed us to find correlations between particular elements in black teas. The performed analyses revealed interesting correlations between the concentration of various elements in black teas: K was negatively correlated with Na, Fe, Mn and Cu, K was positively correlated with the content of Ca and Mg. Significant positive correlations between Mn and Fe and Mn and Zn in the studied black tea samples were also revealed. It was shown that mineral composition may be a significant factor regarding the origin of the black tea, not only considering the country, but also the region or province.

Background Extracts from medicinal plants with phytochemicals with known antimicrobial properties can be an effective adjunct in the complex treatment of infectious diseases. This study aimed to evaluate the antimicrobial activity of wormwood extracts collected in Kazakhstan (Artemisia gmelinii Weber ex Stechm.), along with their phytochemical analysis. Methods The ethanolic and chloroform extracts were subjected to HPLC combined with quadrupole time-of-flight mass spectrometry method. For quantitative assessment of antimicrobial activity, minimal inhibitory concentration (MIC) of the tested extracts was determined by micro-dilution broth method for the panel of the reference microorganisms. Minimal bactericidal concentration (MBC) or minimal fungicidal concentration (MFC) were also determined. Results LC/MS analysis showed the presence of 13 compounds in the tested extracts, including flavonoids: apigenin, luteolin, rutin, two O-methylated flavonols (isorhamnetin, rhamnazine), coumarin compounds (umbelliferone, scopoletin and scopolin (scopoletin 7-glucoside), 3-hydroxycoumarin and 4-hydroxycoumarin), chlorogenic acid and two dicaffeoylquinic acid isomers. Quantitative HPLC analysis showed that umbelliferone was dominant in the chloroform extract while chlorogenic acid was identified as a main compound in the ethanolic extract. The antibacterial and antifungal activity of chloroform and ethanolic extracts was comparable. The most sensitive were the Gram-positive bacteria represented by staphylococci, Micrococcus luteus and Bacillus spp. (MIC = 1.25–5 mg/ml) and yeasts represented by Candida spp. (MIC = 2.5–5 mg/ml), irrespective of the assayed extract. Conclusions Extracts of wormwood Artemisia gmelinii have shown a wide spectrum of antibacterial and antifungal activity. Luteolin, rutin, isorhamnetin and scopolin were identified in A. gmelinii species for the first time. The determining of the most potential compounds of Artemisia gmelinii can be used to develop effective antibacterial and antifungal agents.

Three metal complexes with empirical formulae [Mn(theop)2(H2O)4] (1), [Co(theop)2(H2O)4] (2), [Ni(theop)2(H2O)4] (3), (where: theop = theophylline) were synthesized and characterized by elemental analysis, FTIR- spectroscopy and thermal decomposition techniques. Their crystal structures were determined by single crystal Xray diffraction analysis. Complexes are isomorphous and crystallise in the monocyclic space group P21/c. Their thermal behavior was studied by TGA methods under non-isothermal condition in air. Upon heating all compounds decompose progressively to metal oxides, which are the final products of pyrolysis. Furthermore, antimicrobial and antioxidant activity of the complexes was examined. Keywords: Metal complexes, Thermal investigation, IR spectra, Alkaloids, Theophylline, Antioxidant activity, Biological activity

Here we report studies on the synthesis of 12 new heterocyclic derivatives that differ in three structural motifs and the simultaneous evaluation of the impact of these three variables on the biological properties. The examined compounds are based on rhodanine and 2-thiohydantoin cores equipped with hydrogen or carboxymethyl substituents at the N-3 position and linked to a triphenylamine moiety through 1,4-phenylene, 1,4-naphthalenylene and 1,9-anthracenylene spacers at the C-5 position of the heterocycles. All the compounds were synthesized very quickly, selectively and in high yields according to the developed microwave-assisted Knoevenagel condensation protocol, and they were characterized thoroughly with NMR, FT-IR and ESI-HRMS techniques. The derivatives were tested for their activity against selected strains of Gram-positive and Gram-negative bacteria and yeast. Two compounds showed good activity against Gram-positive bacteria, and all of them showed low cytotoxicity against three cell lines of the human immune system. Based on membrane permeability assays it was demonstrated that the active compounds do not penetrate the cell membrane, and thus they must act on the bacterial cell surface. Finally, we proved that the evaluated structure modifications had a synergistic effect and the simultaneous presence of a 1,4-phenylene spacer and carboxymethyl group at N-3 caused the highest boost in antimicrobial activity.

The chemical composition of the hydroethanolic extracts (60% v/v) from the aerial parts of Thymus marschallianus Willd (TM) and Thymus seravschanicus Klokov (TS) from Southern Kazakhstan flora was analyzed together with their hexane fractions. Determination of antibacterial, antifungal and antioxidant activities of both extracts was also performed. RP-HPLC/PDA and HPLC/ESI-QTOF-MS showed that there were some differences between the composition of both extracts. The most characteristic components of TM were rosmarinic acid, protocatechuic acid, luteolin 7-O-glucoside, and apigenin 7-O-glucuronide, while protocatechuic acid, luteolin 7-O-glucoside, luteolin 7-O-glucuronide, and eriodictyol predominated in TS. The content of polyplenols was higher in TS than in TM. The GC-MS analysis of the volatile fraction of both examined extracts revealed the presence of thymol and carvacrol. Additionally, sesquiterpenoids, fatty acids, and their ethyl esters were found in TM, and fatty acid methyl esters in TS. The antioxidant activity of both extracts was similar. The antibacterial activity of TS extract was somewhat higher than TM, while antifungal activity was the same. TS extract was the most active against Helicobacter pylori ATCC 43504 with MIC (minimal inhibitory concentration) = 0.625 mg/mL, exerting a bactericidal effect. The obtained data provide novel information about the phytochemistry of both thyme species and suggest new potential application of TS as a source of bioactive compounds, especially with anti-H. pylori activity.

The continually evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a vast number of either acute or chronic medical impairments of a pathophysiology that is not yet fully understood. SARS-CoV-2 tropism for the organs is associated with bilateral organ cross-talks as well as targeted dysfunctions, among which acute kidney injury (AKI) seems to be highly prevalent in infected patients. The need for efficient management of COVID-related AKI patients is an aspect that is still being investigated by nephrologists; however, another reason for concern is a disturbingly high proportion of various types of kidney dysfunctions in patients who have recovered from COVID-19. Even though the clinical picture of AKI and COVID-related AKI seems to be quite similar, it must be considered that regarding the latter, little is known about both the optimal management and long-term consequences. These discrepancies raise an urgent need for further research aimed at evaluating the molecular mechanisms associated with SARS-CoV-2-induced kidney damage as well as standardized management of COVID-related AKI patients. The following review presents a comprehensive and most-recent insight into the pathophysiology, clinical manifestations, recommended patient management, treatment strategies, and post-mortem findings in patients with COVID-related AKI.

In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole], X = BF4− (3), SbF6− (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.

Piper spices represent an inexhaustible reservoir of bioactive compounds that may act as drug leads in natural product research. The aim of this study was to investigate a series of methanolic fruit extracts obtained from P. nigrum (black, green, white and red), P. longum and P. retrofractum in comparative phytochemical and multi-directional biological (antimicrobial, antioxidant, anti-enzymatic and anti-melanogenic) assays. The metabolite profiling revealed the presence of 17 piperamides, with a total content of 247.75–591.42 mg piperine equivalents/g. Among the 22 tested microorganism strains, Piper spices were significantly active (MIC &lt, 0.1 mg/mL) against the anaerobes Actinomyces israelii and Fusobacterium nucleatum. The antioxidant and anti-enzymatic activities were evidenced in DPPH (10.64–82.44 mg TE/g) and ABTS (14.20–77.60 mg TE/g) radical scavenging, CUPRAC (39.94–140.52 mg TE/g), FRAP (16.05–77.00 mg TE/g), chelating (0–34.80 mg EDTAE/g), anti-acetylcholinesterase (0–2.27 mg GALAE/g), anti-butyrylcholinesterase (0.60–3.11 mg GALAE/g), anti-amylase (0.62–1.11 mmol ACAE/g) and anti-glucosidase (0–1.22 mmol ACAE/g) assays. Several Piper extracts (10 μg/mL) inhibited both melanin synthesis (to 32.05–60.65% of αMSH+ cells) and release (38.06–45.78% of αMSH+ cells) in αMSH-stimulated B16F10 cells, partly explained by their tyrosinase inhibitory properties. Our study uncovers differences between Piper spices and sheds light on their potential use as nutraceuticals or cosmeceuticals for the management of different diseases linked to bacterial infections, Alzheimer’s dementia, type 2 diabetes mellitus or hyperpigmentation.

Derivatives of 4-methyl-1,6-diphenylpyrimidine-2(1H)-selenone show very strong antimicrobial activity. In order to extend the current knowledge about the features responsible for the biological activity, crystal structure analyses are presented for 4-methyl-1-(2-methylphenyl)-6-phenylpyrimidine-2(1H)-selenone (1), 4-methyl-1-(3-methylphenyl)-6-phenylpyrimidine-2(1H)-selenone (2), 4-methyl-1-(4-methylphenyl)-6-phenylpyrimidine-2(1H)-selenone (3) (all C18H16N2Se) and 1-(4-chlorophenyl)-4-methyl-6-phenylpyrimidine-2(1H)-selenone (4) (C17H13ClN2Se). Furthermore, the antibacterial and antifungal activities of these compounds were evaluated. All the presented derivatives crystallize in the space group P21/c with one molecule in the asymmetric unit. The molecular geometries differ slightly in the mutual orientation of the rings. The packing of molecules in the crystals is dominated by C—H...N and C—H...Se intermolecular interactions. Additionally, in the crystal structure of 4, C—H...Cl intermolecular interactions are observed. The introduction of a methyl or chlorine substituent improves the biological activity, while its position significantly affects biological activity only in case of the chlorine substituent.

Five complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) with non-steroidal anti-inflammatory drug, flufenamic acid were synthesized: (1) [Mn3(fluf)6EtOH)(H2O)]·3EtOH, (2) [Co(fluf)2(EtOH)(H2O)]·H2O, (3) [Ni(fluf)2(EtOH)(H2O)]·H2O, (4) [Cu(fluf)2·H2O], (5) [Zn(fluf)2·H2O]. All complexes were characterized by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The crystal structure of 1 was determined by the single crystal X-ray diffraction technique. It crystallizes in the triclinic space group P with three independent Mn(II) cations, six coordinated flufenamato ligands augmented with water and ethanol molecules in the inner coordination sphere. In this crystal, manganese atoms are multiplied by symmetry and form infinite, polymeric chains which extend along the [001] dimension. The Hirshfeld Surface analysis revealed changes in interaction assemblies around all metal centers. The antioxidant and antimicrobial activities were established for all complexes and free ligand for comparison. All compounds exhibit good or moderate bioactivity against Gram-positive bacteria and yeasts.

Three metal complexes of mefenamato ligand 1 were synthesized: [Co2(mef)4(EtOH)2(H2O)4]: 2, [Co(mef)2(MeOH)4]∙2MeOH: 3, and [Ni(mef)2(MeOH)4]∙2MeOH: 4. Their compositions and properties were investigated by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures were determined by the single crystal X-ray diffraction technique. Additionally, their antioxidant and antimicrobial activity were established, thus proving good/moderate bioactivity against Gram-positive bacteria and yeasts. In the crystal structure of 2, an apical water molecule is shared between two adjacent cobalt(II) ions, resulting in the formation of a polymeric chain extending along the [100] direction. Meanwhile, structures 3 and 4 have strong intermolecular hydrogen bonds with diverse topologies that yield unique quasi-isostructural arrangements. The packing topology is reflected by the Hirshfeld surface analysis of intermolecular contacts.

Two metal complexes of theophylline were synthesized. Namely, 1 with the formula [Cu(theop)2(H2O)3]&middot, 2H2O and 2, [Zn(theop)2]∙H2O (where: theop = theophylline ion). Their properties were thoroughly investigated by the elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) that were augmented by antimicrobial and antioxidant analyses. Their radical scavenging ability (RSA) is notably higher than that of a pure theophylline itself. Similarly to theophylline complexes already studied by us 3, [Mn(theop)2(H2O)4] 4, [Co(theop)2(H2O)4] and 5, [Ni(theop)2(H2O)4] title compounds are inactive against Gram-negative bacteria, but they show moderate or mild activity against Gram-positive rods. The low temperature, single crystal X-ray diffraction technique determines the crystal structure of 1. Its supramolecular crystal topology is affected by the unique, double palindrome water chain that formed by two conserved and a sole coordinated water molecules. Crystal packing arrangements were characterized by fingerprint plots that were derived from the Hirshfeld surfaces (HS), as calculated for all structures in the series 1, 3, 4, 5.

The main compounds in both extracts were gluconasturtiin, 4-methoxyglucobrassicin and rutoside, the amounts of which were, respectively, determined as 182.93, 58.86 and 23.24 mg/100 g dry weight (DW) in biomass extracts and 640.94, 23.47 and 7.20 mg/100 g DW in plant herb extracts. The antioxidant potential of all the studied extracts evaluated using CUPRAC (CUPric Reducing Antioxidant Activity), FRAP (Ferric Reducing Ability of Plasma), and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays was comparable. The anti-inflammatory activity of the extracts was tested based on the inhibition of 15-lipoxygenase, cyclooxygenase-1, cyclooxygenase-2 (COX-2), and phospholipase A2. The results demonstrate significantly higher inhibition of COX-2 for in vitro cultured biomass compared with the herb extracts (75.4 and 41.1%, respectively). Moreover, all the studied extracts showed almost similar antibacterial and antifungal potential. Based on these findings, and due to the fact that the growth of in vitro microshoots is independent of environmental conditions and unaffected by environmental pollution, we propose that biomass that can be rapidly grown in RITA&reg, bioreactors can serve as an alternative source of bioactive compounds with valuable biological properties.

The determined structure of benzyl methyl (3,4-dichlorobenzoyl)carbonohydrazonodithioate, C16H14Cl2N2OS2, has monoclinic (P21/c) symmetry. It is of interest with respect to antibacterial properties. A set of 24 dithioesters was examined in respect of their structural and antibacterial properties. Our studies show that the substitution of the aromatic ring with the hydroxyl group in the ortho position influences strongly the biological activity of the studied compounds against the tested strains.

Muscle damage in Duchenne muscular dystrophy (DMD) caused by the lack of dystrophin is strongly linked to inflammation. Heme oxygenase-1 (HO-1; Hmox1) is an anti-inflammatory and cytoprotective enzyme affecting myoblast differentiation by inhibiting myomiRs. The role of HO-1 has not been so far well addressed in DMD.In dystrophin-deficient mdx mice, expression of Hmox1 in limb skeletal muscles and diaphragm is higher than in wild-type animals, being consistently elevated from 8 up to 52 weeks, both in myofibers and inflammatory leukocytes. Accordingly, HO-1 expression is induced in muscles of DMD patients. Pharmacological inhibition of HO-1 activity or genetic ablation of Hmox1 aggravates muscle damage and inflammation in mdx mice. Double knockout animals (Hmox1

Hyssopus officinalis L. is a common plant that is most usually found in three color forms - f. cyaneus (blue), f. ruber Mill. (purple/pink) and f. albus Alef (white). In the present work, we evaluated the chemical composition and antimicrobial activity of essential oils obtained from Polish-sourced white- and pink-flowered H. officinalis. Gas chromatography-mass spectrometry analysis of the essential oil has shown that both forms of color have a different content of main components. The principle essential oil component of white-flowered H. officinalis L. was pinocamphone (51%), while pink-flowered H. officinalis L. contained almost equal amounts of pinocamphone (28.8%) and isopinocamphone (21.9%). Of note, the essential oil of the pink form was more active against Grampositive bacteria, especially against Bacillus subtilis.

In this work, the synthesis of a group of photoactive materials based on zirconium(IV) phthalocyanine out-of-plane substituted with two fragments of L-arginine is described. The studied group contained the phthalocyanine (Pc) complex, complex immobilized on graphite oxide (GO) flakes, composite of GO-Pc with silver nanoparticles, and GO-Pc being a component of dental filling cement. The structural, compositional, morphological, and optical properties of the materials were studied using, among others, scanning electron microscopy, X-ray diffractometry, and optical spectroscopies (UV–Vis absorption, FTIR, Raman, and photoluminescence). The photoactivity of all materials was confirmed when they were exposed to broadband red light, observed as reactive oxygen species generation that was the highest for the Pc complex, lower for the GO-Pc samples, and the lowest but still present, in the case of GO-Pc-modified cement. The bioactivity of the GO-Pc and GO-Pc-Ag samples was tested against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) bacteria strains showing the highest action against S. aureus and a slight impact of the light irradiation. The comparison of cytotoxicity tests performed for GO-Pcs with Pc complexes substituted with different ligands showed that the GO with L-arginine derivative of PcZr had the lowest toxicity.

The anti-H. pylori properties of 26 different commercial essential oils were examined in vitro by MIC (minimal inhibitory concentration) determination for the reference strain H. pylori ATCC 43504. We selected 9 essential oils with different anti-Helicobacter activities and established their phytochemical composition and urease inhibition activities. Phytochemical analysis of the selected essential oils by GC-MS method and antioxidant activity were performed. The phenol red method was used to screen the effect of essential oils on urease activity expressed as IC50 (the half of maximal inhibitory concentration). The most active essential oils, with MIC = 15.6 mg/L, were thyme, lemongrass, cedarwood and lemon balm oils, MIC = 31.3 mg/L&mdash, oregano oil, MIC = 62.5 mg/L&mdash, tea tree oil, MIC = 125 mg/L&mdash, pine needle, lemon and silver fir oils with bactericidal effect. Urease activity was inhibited by these oils with IC50 ranged from 5.3 to &gt, 1049.9 mg/L. The most active was cedarwood oil (IC50 = 5.3 mg/L), inhibiting urease at sub-MIC concentrations (MIC = 15.6 mg/L). The statistical principal component analysis allowed for the division of the oils into three phytochemical groups differing in their anti-H. pylori activity. To summarize, the activity in vitro of the five essential oils silver fir, pine needle, tea tree, lemongrass, and cedarwood oils against H. pylori was found in this paper for the first time. The most active against clinical strains of H. pylori were cedar wood and oregano oils. Moreover, cedarwood oil inhibited the urease activity at subinhibitory concentrations. This essential oil can be regarded as a useful component of the plant preparations supporting the eradication H. pylori therapy.

An HPLC quadrupole time-of-flight (Q-TOF) MS method was developed for the identification of secondary metabolites in Leonurus turkestanicus V.I. Krecz. et Kuprian. Ethanolic and chloroform extracts from the plant’s aerial parts were tested. A total of 16 compounds (iridoid glycosides, phenylpropanoids, flavonoids, and nitrogen-containing compounds, as well as diterpene acetate derivatives) were identified and tentatively characterized based on (or using) their retention times and UV and Q-TOF-MS data. Previously reported aucubin (1),6-deoxy-8-acetylharpagid(2), and stachydrine(13, 15)and homostachydrine isomers(14, 16)were identified, along with a lavandulifolioside isomer(3),verbascoside(4),rutin(5),3-O-kaempferol rutinoside (6), and an unknown diterpene acetate(8).Compounds3–6were detected for the first time in this plant. Additionally. antimicrobial activity was evaluated. No significant differences were found between ethanolic and chloroform extracts of L. turkestanicus; however, the alcoholic extract showed stronger antifungal activity [minimal inhibitory concentration (MIC) of 2.5–5 mg/mL], whereas the chloroform extract showed stronger activity against the tested spore-forming Bacillus species (MIC 1.25–2.5 mg/mL).

Four new crystal structures of sulfur and selenium analogues of 2[1H]-pyrimidinone derivatives were determined with the use of X-ray diffraction method. The molecular geometry and intermolecular interactions of the investigated molecules were analyzed in order to find the structural features and geometrical parameters, which can be responsible for antimicrobial activities. The influence of chalcogen substituents (sulfur and selenium) on the crystal packing was also studied. The main differences in the molecular structures exist in mutual arrangement of two aromatic rings. The intermolecular interactions in all investigated compounds are similar. Furthermore, the in vitro antibacterial and antifungal activities for these compounds were evaluated. Preliminary investigations have identified two highly potent antibacterial compounds containing selenium atom, which display selectivity towards staphylococci and micrococci. This selectivity was not observed for a control compound used as a drug, namely vancomycin. These compounds possess also good antifungal activity. This is the first report of biological activities of 2[1H]-pyrimidineselenone derivatives.

Derivatives of pyrimidine-2(1H)-selenone are a group of compounds with very strong antimicrobial activity. In order to study the effect of the position of the methoxy substituent on biological activity, molecular geometry and intermolecular interactions in the crystal, three derivatives were prepared and evaluated with respect to their antimicrobial activities, and their crystal structures were determined by X-ray diffraction. The investigated compounds, namely, 1-(X-methoxyphenyl)-4-methyl-6-phenylpyrimidine-2(1H)-selenones (X= 2, 3 and 4 for1,2and3, respectively), C18H16N2OSe, showed very strong activity against selected strains of Gram-positive bacteria and fungi. Two compounds,1and2, crystallize in the monoclinic space groupP21/c, while3crystallizes in the space groupP21/n;1has two molecules in the asymmetric unit and the other two (2and3) have one molecule. The geometries of the investigated compounds differ slightly in the mutual orientations of the aromatic and pyrimidineselenone rings. The O atom in1stabilizes the conformation of the moleculesviaintramolecular C—H...O hydrogen bonding. The packing of molecules is determined by weak C—H...N and C—H...Se intermolecular interactions and additionally in1and2by C—H...O intermolecular interactions. The introduction of the methoxy substituent results in greater selectivity of the investigated compounds.

In search of an effective antibacterial agent that is useful in photodynamic therapy, new derivatives of zirconium(IV) phthalocyanine (ZrPc) complexes were obtained and linked to graphite oxide flakes. In the syntheses of ZrPc derivatives, two bis-axially substituted ligands with terminal amino group and different lengths of linear carbon chain (C4 in 4-aminobutyric acid or C11 in 11-aminoundecanoic acid) were used. The optical properties (absorption and photoluminescence spectra) of ZrPcs and the composites were examined. Broadband red&ndash, near-infrared lamp was tested as an external stimulus to activate ZrPcs and the composites. Optical techniques were used to show generation of singlet oxygen during irradiation. Considering the application of graphite oxide-based materials as bacteriostatic photosensitive additives for endodontic treatment of periapical tissue inflammation, the antibacterial activity was determined on one Escherichia coli strain isolated directly from an infected root canal of a human tooth and one strain with silver and antibiotic resistance. Looking at the obtained results, modified levels of activity toward different bacterial strains are discussed.

The series of new 4-substituted picolinohydrazonamides were synthesized (6-25) and evaluated for tuberculostatic activity. Compounds having a hydrophilic cyclic amine such as morpholine and pyrrolidine at the end of the thiosemicarbazide chain, exhibited the highest antimycobacterial activity. The antimycobacterial activity of compounds 6, 11, and 15 (MIC 0.4–0.8 μg/mL) was higher than that of reference drugs. Moreover, derivative 15 exhibited lower activity against other tested microorganism such as bacteria gram-positive, gram-negative or fungi. Thus, this compound is characterized by the selectivity of antimicrobial activity. Antiproliferative study conducted against human dermal fibroblasts (HDF) and mouse melanoma cell line (B16-F10) revealed low cytotoxicity of compound 15. Conducted research allowed to identify compound 15 as leading for further research.

The search for new tuberculostatics is an important issue due to the increasing resistance ofMycobacterium tuberculosisto existing agents and the resulting spread of the pathogen. Heteroaryldithiocarbazic acid derivatives have shown potential tuberculostatic activity and investigations of the structural aspects of these compounds are thus of interest. Three new examples have been synthesized. The structure of methyl 2-[amino(pyridin-3-yl)methylidene]hydrazinecarbodithioate, C8H10N4S2, at 293 K has monoclinic (P21/n) symmetry. It is of interest with respect to antibacterial properties. The structure displays N—H...N and N—H...S hydrogen bonding. The structure ofN′-(pyrrolidine-1-carbonothioyl)picolinohydrazonamide, C11H15N5S, at 100 K has monoclinic (P21/n) symmetry and is also of interest with respect to antibacterial properties. The structure displays N—H...S hydrogen bonding. The structure of (Z)-methyl 2-[amino(pyridin-2-yl)methylidene]-1-methylhydrazinecarbodithioate, C9H13N4S2, has triclinic (P\overline{1}) symmetry. The structure displays N—H...S hydrogen bonding.

Recently, several studies have been undertaken so as to develop more effective therapeutic approaches towards eradicating Helicobacter pylori. Among these is phytotherapy. The aim of this study was to investigate the activity in vitro of the plant extracts obtained from common herbs cultivated in the Lubelszczyzna region against the reference strain H. pylori ATCC 43504. Among these are thyme herbs, chamomile flowers, peppermint leaves and coneflower herbs. Herein, it was found that the MIC values of the assayed extracts were as follows: the extracts from coneflower herbs showed anti-H. pylori activity with MIC = 31.3-125 μg/ml; the extracts from chamomile flowers demonstrated MIC = 31.3-62.5 μg/ ml; the extracts from peppermint leaves had MIC = 15.6-250 μg/ml; and the extracts from thyme herbs revealed MIC = 15.6-62.5 μg/ml, depending on the solvent used. The most active were the extracts obtained with ethyl acetate or ethanol alcohol absolute 99.8%. These showing MIC within the range of 15.6-62.5 μg/ml, while the lowest activity was observed in case of the extract obtained with 70% aqueous ethanol. This last showing MIC within the range of 62.5-250 μg/ml. The MIC values of essential oil components were 15.6 μg/ml for bisabolol and menthol or 31.3 μg/ml for thymol. The obtained data indicate that the assayed herbs possessed promising anti-H. pylori bioactivity.

To determine serum and urinary selenium (Se) levels in children with and without obesity, and to assess if Se influences the risk of obesity.High-resolution-continuum source-atomic absorption spectrometry (HR-CS-AAS) was used to determine the content of Se in 80 children (age 6-17; 40 boys, 40 girls). Correlations between variables were tested with the use of Spearman's correlation coefficient. U Mann-Whitney test was applied to assess the difference of Se contents in samples. Measured metabolic risk factors (blood pressure, glucose level, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol), age, gender, and BMI were correlated. Logistic regression models were fitted to identify predictors of obesity interacting with selenium content in serum and urine, separately.Obese children, regardless of gender, had lower Se content. Se level in serum (p=0.001, OR 0.74, 95%CI 0.62-0.88) and total cholesterol (p=0.001, OR 1.19, 95%CI 1.08-1.31) were the independent factors significantly influencing the risk of obesity in children. Two separate models were observed for Se in urine: (i) Se level (p0. 0001, OR 0.70, 95%CI 0.58-0.84) and glucose level (p0.0001, OR 1.22, 95%CI 1.10-1.35), and (ii) Se level (p=0.002, OR 0.60 95%CI 0.43-0.83) and total cholesterol level (p=0.003, OR 1.16, 95%CI 1.05-1.28).The current study suggests a possible role of Se in obesity. Further research needs to be performed to check if obese children are an at-risk group for Se deficiency.

BACKGROUND Haemophilus species are the most common microbiota in humans. The aim of this paper was to investigate Haemophilus spp., mainly H. parainfluenzae prevalence, in the upper respiratory tract of chronic hepatitis C (CHC-positive) patients with or without therapy using pegylated interferon alfa and ribavirin. MATERIAL AND METHODS We collected 462 samples from 54 healthy people and 100 CHC-positive patients at various stages: before (group A), during (group B), and after (group C) antiviral therapy. Identification of bacterial isolates including biotypes and antimicrobials susceptibility was accomplished by means of standard microbiological methods. RESULTS In 70.4% of healthy people (control group) and in 27.0% of CHC-positive patients, the presence of haemophili, mainly H. parainfluenzae was observed, and those differences were statistically significant (p

Objective The aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology. Subjects and methods Tests were performed in 40 boys with ASD and 40 healthy boys, aged 2–17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated. Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves. Results 19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician’s general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS. Conclusion The severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required.

s. PHYTOPHARM 2012 M 74 Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] ТОМ 10/2012/2 RECOVERY AND COUNTER-CURRENT SEPARATION OF INDIGO AND INDIRUBIN FROM POLYGONUM TINCTORIUM AIT. LEAVES © Kukula-Koch Wirginia, Glowniak Kazimierz Chair and Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, 1, Chodzki str., 20– 093 Lublin, Poland, virginia.kukula@gmail.com Indigo naturalis (“qing dai”) has been used in traditional Chinese medicine (TCM) as a heat remover. Polygonum tinctorium Ait. belongs to the indigoferous plants together with Indigofera tinctoria l., Isatis indigotica fort., Isatis tinctoria l., and Baphicacanthus cusia brem. its leaves are rich sources of indigo dye, indirubin (a well-known antipsoriatic and antibacterial agent), isatan b, and tryptanthrine. interest in the drug was fostered when activity against myelocitic leukemia of indirubine was discovered. Currently indirubin is known to inhibit cyclin-dependent kinases (Cdk1/cyclin b and Cdk5/p25) as well. Current report is to show the recent advances in the isolation of the precious constituents of P. tinctorium leaf extracts. Suggested by Chinese Pharmacopoeia extraction protocols remain unfavourable, as they employ the usage of highly toxic solvents (chloroform). herewith we present the optimization of extraction process, introducing the 2 % solution of chloral hydrate in dichloromethane as the best from the investigated solvent systems characterized by lower toxicity. Separation of P. tinctorium Ait. metabolites was performed using environmentally friendly separatory technique: fast Centrifugal Partition Chromatography. Among several tested solvent systems, the mixture of n-heptane: ethyl acetate: methanol: water (6:1:6:1) was perceived as the best one. The one led to obtaining of indigo and indirubin of high purity already after the first injection of crude extract. indigo content in P. tinctorium Ait. samples from Taiwan were found to be similar to its quantity determined in the leaves grown in Poland and collected in the late summer. it may prove, that the cultivation of the investigated species could be spread to Europe. A STUDY ON PERIPHERAL UTILIZATION OF GLUCOSE AND ALDOSE REDUCTASE INHIBITORY ACTIVITY OF HOUTTUYNIA CORDATA FRACTIONS © Kumar Manish, Laloo Damiki, Prasad Satyendra K., Hemalatha S Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India, Email: mkumar. rs.phe@itbhu.ac.in The plant Hottuynia cordata, used as a medicinal salad for lowering the blood sugar level in the North Eastern parts of india. Our earlier investigation showed significant antidiabetic effect of H.cordata in streptozotocin induced diabetic rats (1). Therefore, the aim of present study was to evaluate the glucose uptake by isolated rat hemi-diaphragm in an in vitro model. We have also evaluated in vitro aldose reductase inhibitory activity (ARi) and their kinetic profile on different fractions of H. cordata Thunb. (Saururaceae) for their potential use in diabetic cataract. Total phenolic and flavonoids content of different fraction of H.cordata was determined by folin-Ciocalteu and aluminium chloride method respectively. Glucose uptake by isolated rat hemi-diaphragm was evaluated in different fractions of H. cordata using insulin as a reference standard. Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain clear supernatant for the determination of AR activity and protein content. The kinetic studies of inhibitory activity against aldose reductase of different fractions were analyzed using the lineweaver-burk plot with varying concentrations of glyceraldehydes. k m and V max were also estimated. k i value in presence of different fractions was determined by applying Cheng-Prusoff equation (2). The result showed significant level of phenol and flavonoids in ethyl acetate and aqueous fraction compared to hexane and chloroform fraction. Ethyl acetate fraction showed maximum glucose utilization by rat hemidiaphragm and was also found to have the most potent ARi activity which was significant when compared with all other fractions. Their iC 50 values with descending order of activity was reported to be: ethyl acetate [64.62 ± 3.9 μg/ml] > aqueous [90.69 ± 7.5 μg/ml] > hexane [134.59 ± 4.9 μg/ml] > chloroform [151.58 ± 3.3 μg/ml] respectively. from the kinetic studies, it was found that the ethyl acetate fraction showed a non-competitive inhibition while all other fractions showed competitive inhibition. The present study concluded that ethyl acetate fraction of H.cordata exhibited maximum glucose utilization and ARi activity which may be due to the presence of high phenols and flavonoids content. References: (1) kumar M, Prasad Sk, laloo d, hemalatha S. 2011. 12 congress of international Society for Ethnopharmacology, kolkata india, feburary 17–19, Abstract No. SNPSJU0279. (2) daniellou R, Zheng h, Palmer dRJ. 2006. Can J Chem 84: 522–527.

The retention behaviour of eleven derivatives of counarin was investigated by reversed-phase (RP) thin-layer and high performance liquid chromatography. The linear relationships between log k'or RM values and the content of organic modifier in the aqueous mobile phase obtained for wide composition ranges indicate that the plots can be used to determine RMw and log kw values by extrapolation to pure water. The effects of individual substituants on the retention and the correlation between TLC and HPLC data was analysed.

A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4′-(N,N-dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5 position were synthesised and their antibacterial activity was screened. All the rhodanine derivatives showed bacteriostatic or bactericidal activity to the reference gram-positive bacterial strains, but lack of activity to the reference Gram-negative bacterial strains and yeast strains was observed.