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Aim of the study: Both nasal and bronchial epithelial cells have evolved sophisticated mechanisms involved in cellular response to bacterial infection. Recognition of pathogens by TLR receptors activate the NF-κB transcription factor, and lead to production of wide spectrum of cytokines (TNF-α, IL-1β, IL-6 and IL-8). Released by epithelium proinflammatory cytokines intensify migration of macrophages to damaged tissues and modulate their pro-inflammatory functions. Based on traditional use of G. squarrosa aerial parts we hypothesized that successful treatment of cold-related diseases may arise from modulation of the pro-inflammatory functions of respiratory epithelium and human monocytes/macrophages. The biological activity of G. squarrosa extract and grindelic acid were compared with clarithromycin and budesonide used as positive controls.Methods: The expression of surface receptors (TLR-4, IL-10) and expression of adhesive molecules (ICAM-1, VCAM-1, E-selectin) was analyzed with flow cytometry. The macrophage attachment to the epithelial cells was assessed fluorimetrically. The p65 NF-κB concentration and cytokine production was measured spectrophotometrically using enzyme-linked immunosorbent assay. Antibacterial activity was examined by the standard disc-diffusion method and serial dilution method according to CLSI guidelines.Results:G. squarrosa extract and grindelic acid had no antimicrobial effect. However, we noticed significant modulation of pro-inflammatory functions of LPS-stimulated nasal and bronchial epithelium. G. squarrosa extract treatment resulted in decrease of TLR-4 expression and p65 NF-κB concentration and inhibition of cytokines synthesis (IL-8, TNF-α, IL-1β and IL-6) in both cellular models. Additionally, G. squarrosa extract slightly modulated ICAM-1 expression affecting on attachment of macrophages to epithelium. Only G. squarrosa extract was able to stimulate the anti-inflammatory functions of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Grindelic acid, identified as a dominant compound in the plant extract, modulated pro-inflammatory functions of epithelium and macrophages slightly.Conclusion: The obtained results support traditional use of Grindelia squarrosa preparations for a treatment cold-associated diseases symptoms. In our opinion, the observed biological effect of extract may be a consequence of synergistic effect of all compounds present in the extract.

In luminescence thermometry enabling temperature reading at a distance, an important challenge is to propose new solutions that open measuring and material possibilities. Responding to these needs, in the nanocrystalline phosphors of yttrium oxide Y2O3 and lutetium oxide Lu2O3, temperature-dependent emission of trivalent terbium Tb3+ dopant ions was recorded at the excitation wavelength 266 nm. The signal of intensity decreasing with temperature was monitored in the range corresponding to the 5D4 &rarr, 7F6 emission band. On the other hand, defect emission intensity obtained upon 543 nm excitation increases significantly at elevated temperatures. The opposite thermal monotonicity of these two signals in the same spectral range enabled development of the single band ratiometric luminescent thermometer of as high a relative sensitivity as 4.92%/&deg, C and 2%/&deg, C for Y2O3:Tb3+ and Lu2O3:Tb3+ nanocrystals, respectively. This study presents the first report on luminescent thermometry using defect emission in inorganic phosphors.

The increasing challenge of antibiotic resistance stimulates the search for novel antibacterial agents, especially such that would be effective against multi-drug resistant bacterial strains. Fortunately, natural compounds are excellent sources of potentially new drug leads. Particularly interesting in this context are polyether antibiotic salinomycin (SAL) and its semi-synthetic derivatives, as they exhibit large spectrum of bioactivity. We synthesized and evaluated the antibacterial activity of a series of SAL analogs; four singly (2–3, 15, 17) and two doubly modified (16, 18) derivatives were found to show excellent inhibitory activity not only against planktonic Gram(+) bacterial cells, but also towards select strains of methicillin-resistant staphylococci with the MIC values of 1–4 µg mL−1. Of note, the most promising candidates were more effective in preventing bacterial biofilm formation than unmodified SAL and a commonly used antibiotic – ciprofloxacin. Furthermore, we proved that rational modification of C20 hydroxyl of SAL may reduce genotoxic properties of the obtained analogs. Mechanistically, the structure-activity relationship studies suggested that electroneutral transport mechanism could be beneficial in terms of ensuring high antibacterial activity of SAL derivatives.

A total of 14 of 1,5-disubstituted tetrazole derivatives were prepared by reacting appropriate thiourea and sodium azide in the presence of mercury (II) chloride and triethylamine. All compounds were evaluated in vitro for their antimicrobial activity. Derivatives 10 and 11 showed the highest inhibition against Gram-positive and Gram-negative strains (standard and hospital strains). The observed minimal inhibitory concentrations values were in the range of 1–208 μM (0.25–64 μg/ml). Inhibitory activity of 1,5-tetrazole derivatives 10 and 11 against gyrase and topoisomerase IV isolated from S. aureus was studied. Evaluation was supported by molecular docking studies for all synthesized derivatives and reference ciprofloxacin. Moreover, selected tetrazoles (2, 3, 5, 6, 8, 9, 10 and 11) were evaluated for their cytotoxicity. All tested compounds are non-cytotoxic against HaCaT and A549 cells (CC50 ≤ 60 μM).

The spectroscopic properties of YAG:Ti and YAG:Ti,Ln nanocrystalline powders were examined as part of the search for new functional materials devoted to luminescent thermometry. Various temperature-dependent processes occurring in the studied systems were analyzed and the mechanism of absorption and emission of trivalent and tetravalent titanium ions was proposed. The first luminescent thermometer based on the Ti4+/Ti3+ luminescence intensity ratio with maximum sensitivity of 0.71% C–1 is shown. It was shown that the codoping with lanthanide ions enhances the relative sensitivity of YAG:Ti,Ln nanocrystalline luminescent thermometers because of the Ti4+ → Ln3+ energy transfer. The maximal relative sensitivities in the physiological range (2.26% C–1 at 50 °C) were found for YAG:Ti,Nd3+ nanocrystals and the value increases with temperature reaching 3.70% C–1 at 200 °C.

Luminescent and temperature sensitive properties of YAG:Cr3+,Nd3+ nanocrystals were analyzed as a function of temperature, nanoparticle size, and excitation wavelength. Due to numerous temperature-dependent phenomena (e.g. Boltzmann population, thermal quenching, and inter-ion energy transfer) occurring in this phosphor, four different thermometer definitions were evaluated with the target to achieve a high sensitivity and broad temperature sensitivity range. Using a Cr3+ to Nd3+ emission intensity ratio, the highest 3.48% K-1 sensitivity was obtained in the physiological temperature range. However, high sensitivity was compromised by a narrow sensitivity range or vice versa. The knowledge of the excitation and temperature susceptibility mechanisms enabled wise selection of the spectral features found in luminescence spectra for a temperature readout, which enabled the preservation of relatively high temperature sensitivity (>1.2% K-1 max) and extended the temperature sensitivity range from 100 K to 850 K. The size of the nanophosphors had negligible impact on the performance of the studied materials.

Five of thiourea derivatives were prepared using as a starting compound 3-(trifluoromethyl)aniline, 4-chloro-3-nitroaniline, 1,3-thiazol- 2-amine, 2H-1,2,3-triazol-4-amine and commercial isothiocyanates. All compounds were evaluated in vitro for antimicrobial activity. Derivatives 2 and 3 showed the highest inhibition against Gram-positive cocci (standard and hospital strains). The observed MIC values were in the range of 0.5–8 μg/ml. The products effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Inhibitory activity of thioureas 2 and 3 against Staphylococcus aureus topoisomerase IV was studied. The examined compounds were nongenotoxic.

4-Chloro-3-nitrophenylthioureas 1&ndash, 30 were synthesized and tested for their antimicrobial and cytotoxic activities. Compounds exhibited high to moderate antistaphylococcal activity against both standard and clinical strains (MIC values 2&ndash, 64 &mu, g/mL). Among them derivatives with electron-donating alkyl substituents at the phenyl ring were the most promising. Moreover, compounds 1&ndash, 6 and 8&ndash, 19 were cytotoxic against MT-4 cells and various other cell lines derived from human hematological tumors (CC50 &le, 10 &mu, M). The influence of derivatives 11, 13 and 25 on viability, mortality and the growth rate of immortalized human keratinocytes (HaCaT) was observed.

A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with appropriate aryl/alkylisothiocyanates in anhydrous media. The structures of the newly synthesized compounds were confirmed by spectroscopic analysis and the molecular structures of 8 and 28 were confirmed by X-ray crystallography. All obtained compounds were tested for antimicrobial activity against Gram-positive cocci, Gram-negative rods and for antifungal activity. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Compound 6 showed significant inhibition against Gram-positive cocci and had inhibitory effect on the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase supercoiling activity. Compounds were tested for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses, including HIV-1 and other several important human pathogens. Interestingly, derivative 8 showed potent activity against HIV-1 wild type and variants bearing clinically relevant mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum activity, proving to be active against positive- and negative-sense RNA viruses.

Monensin A (MON) is a polyether ionophore antibiotic, which shows a wide spectrum of biological activity. New MON derivatives such as double-modified ester-carbonates and double-modified amide-carbonates were obtained by a new and efficient one-pot synthesis with triphosgene as the activating reagent and the respective alcohol or amine. All new derivatives were tested for their antiproliferative activity against two drug-sensitive (MES-SA, LoVo) and two drug-resistant (MES-SA/DX5, LoVo/DX) cancer cell lines, and were also studied for their antimicrobial activity against different Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. For the first time, the activity of MON and its derivatives against MES-SA and MES-SA/DX5 were evaluated.

A total of 31 of thiourea derivatives was prepared reacting 3-(trifluoromethyl)aniline and commercial aliphatic and aromatic isothiocyanates. The yields varied from 35% to 82%. All compounds were evaluated in vitro for antimicrobial activity. Derivatives 3 , 5 , 6 , 9 , 15 , 24 and 27 showed the highest inhibition against Gram-positive cocci (standard and hospital strains). The observed MIC values were in the range of 0.25–16 μg/ml. Inhibitory activity of thioureas 5 and 15 against topoisomerase IV isolated from Staphylococcus aureus was studied. Products 5 and 15 effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis . Moreover, all obtained thioureas were evaluated for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses. Compounds 5, 6 , 8–12 , 15 resulted cytotoxic against MT-4 cells (CC 50 ≤ 10 μM).

A series of 10 amine derivatives of colchicine have been obtained with high yields by modification at C(10)-OCH3 position of C-ring and characterized by spectroscopic methods. In vitro cytotoxicity has been evaluated against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX), as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). From among the compounds tested the most active is colchicine derivative 2h with bis(2-methoxyethyl)amine substituent which is active in nanomolar to submicromolar concentrations and is several times more cytotoxic than cisplatin and doxorubicin. This compound is also effective against the methicillin-resistant Staphylococci strains.

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

Ethnopharmacological relevance Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model. Materials and Methods The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages. Results The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition). Conclusions The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration.

A series of novel amino acid and dipeptide derivatives of neocryptolepine were synthesized and tested for their antimicrobial, antifungal and antiproliferative activity in vitro against cancer cell lines (KB, A549, MCF-7, LoVo) and normal mice fibroblast cells (BALB/3T3). Biological evaluation revealed that almost all of the new compounds displayed high antiproliferative activity against the tested cells and moderate to potent antibacterial activities. Interestingly, these compounds were active against Candida albicans biofilms at doses significantly lower than those required against free-floating planktonic fungal cells. The most promising compounds are derivatives with glycine and L-proline as a substituent both at 2 and at 9 position of 5H-indolo[2,3-b]quinoline. In general, these new compounds (2a, 3a, 6a and 7a) showed the highest dual action against cancer lines and infectious pathogenic microbes in vitro.

A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).

Ellagitannin-rich plant materials are used as popular remedies in the treatment of various inflammatory diseases. Urolithins are gut microbiota metabolites of ellagitannins and are considered responsible for in vivo health effects. Various natural products have been studied that are known sources of urolithins. However, few studies have focused on the metabolism of ellagitannin molecules. The aim of the study was to examine the metabolic fate of select ellagitannins using ex vivo cultures of human gut microbiota. Fifteen monomeric and dimeric ellagitannins, 1-O-galloyl-4,6-(S)-HHDP-β-d-glucose (2), pedunculagin (3), potentillin (4), casuarictin (5), coriariin B (6), vescalagin (7), castalagin (8), stachyurin (9), casuarinin (10), stenophyllinin A (11), stenophyllanin A (12), salicarinin A (13), gemin A (14), agrimoniin (15), and oenothein B (16), and ellagic acid (1) were studied. The formation of the metabolites in ex vivo human microbiota cultures was monitored using UHPLC-DAD-MS/MS. Ellagitannins possessing hexahydroxydiphenoyl moieties were metabolized to 6H-dibenzo[b,d]pyran-6-one derivatives, i.e., urolithins. The observed differences in amounts of produced urolithins indicated that the individual microbiota composition and type of ingested ellagitannins could determine the rate of urolithin production. When the oral ingestion of natural products containing ellagitannins with hexahydroxydiphenoyl groups is considered, the formation of urolithins and their bioactivity should be addressed.

The aim of this study was comparison of antioxidant, anti-inflammatory, and antimicrobial activity, as well as chemical composition of extracts of Tropaeolum majus L. herb. Aqueous and hydroethanolic extracts derived from dried and freeze-dried nasturtium herb, prepared both at room temperature and at 90 °C, were studied. In the studies there were no significant differences between antioxidant activity of the extracts. All extracts showed scavenging activity against all the examined reactive species in a concentration-dependent manner. The strongest scavenging activity they showed against reactive nitrogen species, NO (SC50 4.54 ± 0.26–10.90 ± 1.39 μg/mL) and ONOO − (SC50 2.49 ± 1.50–6.37 ± 1.86 μg/mL). Among reactive oxygen species, they showed strong scavenging activity against H 2 O 2 (SC50 14.90 ± 3.91–38.63 ± 9.28 μg/mL). Scavenging activity against O 2 − was weaker, while against HClO the extracts showed very weak activity, practically at the level of statistical error. Against synthetic radical – DPPH scavenging activity of the tested extracts was negligible. The extracts demonstrated stronger antioxidant activity in ex vivo experiment on human neutrophils. The extracts showed no inhibitory activity on hyaluronidase, but at a concentration of 50 μg/mL they inhibited the activity of COX1 by approximately 60%. Lack of antimicrobial activity of the extracts seems to be associated with a low content of benzyl isothiocyanate. The aqueous extracts were characterized by the presence of esters of quinic acid with cinnamic acids (chlorogenic acids, p-coumaroylquinic acids) and the presence of flavonoids. Meanwhile the hydroethanolic extracts were mainly rich in the above mentioned acid esters.

In a reaction of hydrazides of cyclohexylacetic acid 1 and phenylacetic acid 2 with isothiocyanates, respective thiosemicarbazide derivatives 3–18 were obtained. Further cyclization with 2% NaOH led to the formation of 5-(cyclohexylmethyl/benzyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones 19–34. Structures of all new products were confirmed by analytical and spectroscopic methods. All compounds were screened for their in vitro activity against some species of bacteria and fungi. [Supplementary materials are available for this article. Go to the publisher's online edition ofPhosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional figures and tables.]

A series of new Monensin A dimers linked by diurethane moiety were synthesised and their molecular structures were studied using ESI-MS, FT-IR, 1 H and 13 C NMR and PM5 methods. The results showed that the compounds form a pseudo-cyclic structure stabilized by three intramolecular hydrogen bonds and the sodium cation was coordinated by five oxygen atoms of polyether skeleton of Monensin moiety. The NMR and FT-IR data of complexes of Monensin urethane sodium salts demonstrated that within the pseudo-cyclic structure the carbonyl oxygen atom of the urethane group did not coordinate the sodium cation. Monensin urethanes were tested in vitro for the activity against Gram-positive and Gram-negative bacteria and fungi as well as against a series of clinical isolates of Staphylococcus : methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). The most active compound against MRSA and MSSA was 1,4-phenylene diurethane of Monensin with MIC 10.4–41.4 μmol/L).

Two new complexes of the ionophore antibiotic Lasalocid acid (LAS) with phenylamine (PhA) and butylamine (BuA) were synthesized and their molecular structures were studied using single crystal X-ray diffraction and spectroscopic methods. In the solid state both amines are protonated and all NH 3 + protons are hydrogen bonded to etheric, hydroxyl and carboxylic oxygen atoms of the LAS anion. In chloroform solutions the structure observed in the crystal of LAS–BuA complex is preserved and an equilibrium between the LAS–PhA complex and dissociated Lasalocid acid and phenylamine is observed. In vitro antimicrobial tests of the complexes showed a significant activity towards some strains of Gram-positive bacteria. For the first time Lasalocid acid and its complexes with amines were tested in vitro for cytotoxic activity against human cancer cell lines: A-549 (lung), MCF-7 (breast), HT-29 (colon) and mouse cancer cell line P-388 (leukemia). We found that LAS and its complexes are strong cytotoxic agents towards all tested cell lines. The cytostatic activity of the compounds studied is greater than that of cisplatin, indicating that Lasalocid and its complexes are promising candidates for new anticancer drugs.

A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The 1H NMR, 13C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against Gram-positive cocci, Gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against Gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1–13) were examined for cytotoxicity, antitumor, and anti-HIV activity.

The unexpectedly stable benzotriazole ester of salinomycin (SAL-HOBt) – an intermediate product of the amidation reaction of salinomycin has been isolated and structurally characterised (using a single crystal) by X-ray, FT-IR, NMR and semiempirical methods. The results of the X-ray and spectroscopic studies demonstrated that this intermediate ester exist in the solid state and in solution exclusively as the stable O–acyl form. The molecular structure of SAL-HOBt is stabilised by relatively weak intramolecular hydrogen bonds. The PM5 calculation of possible structures of SAL-HOBt has shown that the O–acyl form is more energetically favourable than its N–oxide–N–acyl isomers. The antimicrobial tests show that SAL-HOBt is active against Gram-positive bacteria and clinical isolates methicillin-resistant Staphylococcus aureus (MIC = 1–2 μg/ml).

For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.

A new amide of monensin A with 4-aminobenzo-15-crown-5 (M-AM3) was synthesised and its ability to form complexes with Na+ cations was studied by ESIMS, 1H, 13C and 23Na NMR, FTIR and PM5 semi-empirical methods. ESI mass spectrometry indicates that in the gas phase M-AM3 amide forms complexes of 1:1 and 1:2 stoichiometry with Na+ cations. The formation of such complexes is also confirmed in the acetonitrile solution, in which the existence of equilibrium between two structures A and B is found, of which B structure is dominant. The structures of M-AM3 and its 1:1 and 1:2 complexes with Na+ cations are stabilised by various intramolecular hydrogen bonds, which are discussed in detail. The in vitro biological tests have demonstrated that the new M-AM3 amide shows good activity towards some strains of Gram-positive bacteria (MIC 25–50 μg/ml).

Halogen derivatives of selected 3-benzofurancarboxylic acids were prepared using 6-acetyl-5-hydroxy-2-methyl-3-benzofuranocarboxylic acid as starting material. (1)H-NMR spectra were obtained for all of the synthesized structures, and for compound VI, an X-ray crystal structure was also obtained. All derivatives were tested for antimicrobial activity against a selection of Gram-positive cocci, Gram-negative rods and yeasts. Three compounds, III, IV, and VI, showed antimicrobial activity against Gram-positive bacteria (MIC 50 to 200 microg/mL). Compounds VI and III exhibited antifungal activity against the Candida strains C. albicans and C. parapsilosis (MIC-100 microg/mL).

Four new hydroxy-aminoalkyl derivatives of α,β-unsaturated macrolide-josamycin (2–5) have been synthesised and their structures have been studied by means of 1H and 13C NMR and FT-IR methods. Complete assignment of resonances in the 1H and 13C NMR spectra has been made on the basis of 1H13C HSQC, 1H13C HMBC, 1H1H COSY, 1H1H NOESY 2D experiments. Spectroscopic data indicated that for the derivatives 3 and 4 some equilibrium between two different structures exists in contrast to derivatives 2 and 5. The lowest-energy structures of the new derivatives of josamycin have been calculated and visualised by PM5 method at semi-empirical level of theory, taking into account the NMR and FT-IR data. The most significant differences between the structures of josamycin and its newly synthesised derivatives' were found in the conformation of the macrolide aglycone part and in the mutual orientation of the 4-O-isovalerylmycarosylmycaminose moiety relative to the aglycone part. PM5 semi-empirical calculations indicated that the structures of the new macrolide derivatives are stabilised by rather weak intramolecular hydrogen bonds in agreement with spectroscopic data. Antimicrobial properties of the new derivatives 2–5 as well as those having an acetate group at C-3 (6 and 7) were determined and compared to that of the parent macrolide antibiotic josamycin (1). Copyright © 2010 John Wiley & Sons, Ltd.

Antibacterial and antifungal activity of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives were examined by the disk diffusion method (growth inhibition zone diameter in agar medium). The minimal inhibitory concentrations (MICs) for the most active agents were determined. Title compounds were also evaluated in vitro against HIV-1 virus and their cytotoxicity was determined. Aminoalkanol derivatives exhibited activity against the majority of microorganisms studied.

Four 4-aryl-3-(2-methyl-furan-3-yl)-Δ2-1,2,4-triazole-5-thiones were synthesized by intramolecular cyclization of 4-aryl-1-[(2-methyl-furan-3-yl)carbonyl]thiosemicarbazides in alkaline medium. The antimicrobial activity of the synthesized triazoles was evaluated. Semiempirical calculations of geometries, energies, and QSAR parameters have been determined in the hope of gaining insight into different biological activities of closely related isomers. New RM1 parameterization has been shown to perform very well for this class of compounds.

A new complex of lasalocid acid with allylamine (LAS–AM) is synthesised and studied by X-ray, FT-IR, 1 H NMR and 13 C NMR, ESI MS methods. In the solid state allylamine is protonated and all protons of NH 3 + are hydrogen bonded. We show that in the gas, liquid and solid states lasalocid forms 1:1 complexes with allylamine and that its structures of all states are comparable, which indicates that the complex LAS–AM is very stable. The stability of the LAS–AM complex is achieved by some intra-molecular hydrogen bonds. Due to these interactions the outside of the complex is hydrophobic enabling its transport across the biological membranes. This property of the complex is reflected in its anti-microbial activity, which is discussed.

Antibacterial and antifungal activity of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives were examined by the disc-diffusion method (growth inhibition zone diameter in agar medium). The MIC’s for the most active agents were determined. Title compounds were also evaluated in vitro against representatives of different virus classes. Most of the tested compounds exhibit activity against CVB-2 virus.

A complex between a new N-phenylamide of monensin A (M-AM1) and sodium chloride has been synthesised and studied by X-ray diffraction and FT-IR spectroscopy. The crystal structure of the complex between M-AM1 and sodium chloride with acetonitrile was examined using X-ray diffraction and discussed in detail. Its structure is stabilised by coordination of the Na+ cation with oxygen atoms. The Na–O bond lengths are between 2.382(2) and 2.562(2) A. The chloride anion is involved in a weak intermolecular hydrogen bond between different species forming a supramolecule. The ESI-MS spectra indicate that the amide forms stable complexes of exclusively 1:1 stoichiometry with Na+ cations. The FT-IR spectrum of the crystal is consistent with the results obtained by the X-ray study and provides spectroscopic evidence for the complex formation. Due to its specific structural properties N-phenylamide of monensin A efficiently binds sodium chloride. The result of the PM5 semiempirical calculation is in agreement with the spectroscopic data and allows visualisation of the structure of the M-AM1–Na+ complex. The new amide of monensin A has been additionally tested in view of its antimicrobial properties. It shows great activity towards some strains of Gram-positive bacteria (MIC = 6.25–12.5 μg/ml).

A series of 13 new ether-linked derivatives of 2,2-dimethyl-2,3-dihydro-7-benzo[b]furanol have been designed and synthesized. Ten of them were evaluated for their potential antimicrobial activity against some Gram-positive and Gram-Negative bacteria and fungi of the Candida species.

Anhydrides, imides, N-ethylimides, N-hydroxyimides and N-aminoimides of 1,4,5,6-tetramethyl-bicyclo[5.2.1.0 2,6 ]hept-5-ene-2,3-dicarboxylic acid, 1,4,5,6,7-pentamethyl-bicyclo[5.2.1.0 2,6 ]hept-5-ene-2,3-dicarboxylic acid and 7-ethyl-1,4,5,6-tetramethyl-bicyclo[5.2.1.0 2,6 ]hept-5-ene-2,3-dicarboxylic acid were obtained. Antimicrobial activity of the newly obtained derivatives was tested against selected Gram-positive and Gram-negative bacteria and fungi of the Candida species. The structures of obtained compounds and their antimicrobial activity were compared. Structure of 1b, 2b and 1e were determined by an X-ray analysis.

A new lasalocid 1-naphthylmethyl ester (NAFA) has been synthesised and studied by X-ray, 1 H NMR, 13 C NMR, FT-IR, UV–vis, fluorescence as well as by PM5 semiempirical methods. The crystals of NAFA belong to the monoclinic system with the space group P2 1 with a = 13.4251(5) A, b = 17.1064(7) A, c = 18.5454(7) A, β = 98.924(4)° and Z = 4. Two conformers of NAFA have been observed for two symmetry-independent molecules in different crystal environments. The molecular conformation of NAFA is partially stabilized by three intramolecular hydrogen bonds, in which the keto group is not involved. The FT-IR spectrum of NAFA in chloroform indicates that in this solvent the equilibrium between two structures of NAFA is realized. In one of the structures, the keto group is hydrogen bonded while in the other one this group is not involved in any hydrogen bond. The two structures of NAFA are discussed in detail. The new ester which has been additionally tested for its antimicrobial properties shows a certain activity against Gram-positive bacteria, however no activity against Gram-negative bacteria and Candida .

A new method to synthesize novel esters of Lasalocid acid 2–5 and of Monensin A, 7–9 (semi-synthetic di- and tripodands) is described. These new compounds are characterized by spectroscopic and microbiological methods. 2008 Elsevier Ltd. All rights reserved.

A new quaternary ammonium compound, bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride (4), was synthesized. The compound was investigated for antibacterial activity, including Gram-positive cocci and Gram-negative rods, and antifungal activity. Compound 4 showed significant inhibition against Staphylococcus aureus. Research was carried out over 4 standard strains and 40 hospital strains. Elementary analysis and/or MS, (1)H NMR and (13)C NMR spectra confirmed the identity of the products. The molecular structure of 3 was determined by an X-ray analysis.

A series of nineteen new thiourea and urea derivatives of 10-isopropyl-8-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione, 1-isopropyl-7-methyl-4-azatricyclo[5.2.2.0(2,6)]undec-8-ene-3,5-dione and 1,7,8,9,10-pentamethyl-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared and studied by (1)H-NMR. The compound k1a (1-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.0(2,6)]dec-8-en-4-yl)-3-phenyl-urea) was tested for pharmacological activity on animal central nervous system (CNS). The activities of synthesized compounds were evaluated for their cytotoxicity and anti-HIV-1 activity in MT-4 cells. Antimicrobial activity of the newly obtained derivatives was tested against some Gram-positive and Gram-negative bacteria and fungi of the Candida species.

A series of new thiourea derivatives of 1,3-thiazole have been synthesized. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds were also tested for their in vitro tuberculostatic activity against the Mycobacterium tuberculosis H37Rv strain, as well as two 'wild' strains isolated from tuberculosis patients. Compounds 3 and 9 showed significant inhibition against Gram-positive cocci (standard strains and hospital strain). The range of MIC values is 2-32 µg/mL. Products 3 and 9 effectively inhibited the biofilm formation of both methicillin-resistant and standard strains of S. epidermidis. The halogen atom, especially at the 3rd position of the phenyl group, is significantly important for this antimicrobial activity. Moreover, all obtained compounds resulted in cytotoxicity and antiviral activity on a large set of DNA and RNA viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and other several important human pathogens. Compound 4 showed activity against HIV-1 and Coxsackievirus type B5. Seven compounds resulted in cytotoxicity against MT-4 cells (CC50

For the first time, a series of tertiary amides of polyether antibiotic—Salinomycin have been obtained and screened for their antibacterial activity against different strains of bacteria, including Bacillus anthracis and clinical methicillin-resistant Staphylococcus epidermidis (MRSE). Moreover, biofilm inhibition of MRSE and genotoxicity tests against Bacillus subtilis have been performed. Our studies show that Salinomycin and its some derivatives are active against tested bacteria and exhibited definitely bacteriostatic, not bactericidal activity.

A set of 21 thiourea derivatives were prepared through reacting 3-amino-1H-1,2,4-triazole with the commercial aliphatic and aromatic isothiocyanates. The aliphatic isothiocyanate was used as reagent leading to substitution on NH atom of 3-aminotriazole ring, whereas the triazole amino group was substituted when isothiocyanate group was bonded to the Csp2 hybridized atom, e.g. an aryl or C=O fragment. All compounds were evaluated in vitro for the antimicrobial activity. The derivatives 1, 2, 4, 8, 9, 10 and 12 showed the highest inhibition against Gram-positive cocci (S. aureus and S. epidermidis). The observed MIC values were in the range of 4-32 μg/mL. Compounds were also tested for their in vitro antimicrobial activity against the hospital methicillin-resistant strains of S. aureus. The observed MIC values varied from 4 to 64 μg/mL. The products 4 and 10 effectively inhibited the formation of biofilms of the methicillin-resistant and standard strains of S. epidermidis. The compound 10 was found to be more promising with IC50 values of 2-6 μg/mL as compared to the control. Moreover, the cytotoxicity against the MT-4 cells of all studied thioureas was evaluated. The compound 18 was significantly cytotoxic (CC50 = 8 μM).

Metallic monodisperse copper nanoparticles at a relatively high concentration (300 ppm CuNPs) have been synthesized by the reduction of copper salt with hydrazine in the aqueous SDS solution. The average particles size and the distribution size were characterized by Dynamic Light Scattering (DLS), Nanosight-Nanoparticle Tracking Analysis (NTA). The morphology and structure of nanoparticles were investigated using Scanning Electron Microscopy (SEM). The chemical composition of the copper nanoparticles was determined by X-ray Photoelectron Spectroscopy (XPS). Monodisperse copper nanoparticles with average diameter 50 nm were received. UV/vis absorption spectra confirmed the formation of the nanoparticles with the characteristic peak 550 nm. The antimicrobial studies showed that the copper nanoparticles had high activity against Gram-positive bacteria, standard and clinical strains, including methicillin-resistant Staphylococcus aureus, comparable to silver nanoparticles and some antibiotics. They also exhibited antifungal activity against Candida species.