Influence of proline and hydroxyproline as antimicrobial and anticancer peptide components on the silver(I) ion activity: structural and biological evaluation with a new theoretical and experimental SAR approach.

Silver(I) complexes with proline and hydroxyproline were synthesized and structurally characterized and crystal structure analysis shows that the formulas of the compounds are {[Ag2(Pro)2(NO3)]NO3}n (AgPro) (Pro = L-proline) and {[Ag2(Hyp)2(NO3)]NO3}n (AgHyp) (Hyp = trans-4-hydroxy-L-proline). Both complexes crystallize in the monoclinic lattice with space group P21 with a carboxylate bidentate-bridging coordination mode of the organic ligands Pro and Hyp (with NH2+ and COO- groups in zwitterionic form). Both complexes have a distorted seesaw (C2v) geometry around one silver(I) ion with τ4 values of 58% (AgPro) and 51% (AgHyp). Moreover, the results of spectral and thermal analyses correlate with the structural ones. 1H and 13C NMR spectra confirm the complexes species' presence in the DMSO biological testing medium and their stability in the time range of the bioassays. In addition, molar conductivity measurements indicate complexes' behaviour like 1 : 1 electrolytes. Both complexes showed higher or the same antibacterial activity against Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus as AgNO3 (MIC = 0.063 mM) and higher than silver(I) sulfadiazine (AgSD) (MIC > 0.5 mM) against Pseudomonas aeruginosa. In addition, complex AgPro exerted a strong cytotoxic effect against the tested MDA-MB-231 and Jurkat cancer cell lines (IC50 values equal to 3.7 and 3.0 µM, respectively) compared with AgNO3 (IC50 = 6.1 (5.7) µM) and even significantly higher selectivity than cisplatin (cisPt) against MDA-MB-231 cancer cell lines (SI = 3.05 (AgPro); 1.16 (cisPt), SI - selectivity index). The binding constants and the number of binding sites (n) of AgPro and AgHyp complexes with bovine serum albumin (BSA) were determined at four different temperatures, and the zeta potential of BSA in the presence of silver(I) complexes was also measured. The in ovo method shows the safety of the topical and intravenous application of AgPro and AgHyp. Moreover, the complexes' bioavailability was verified by lipophilicity evaluation from the experimental and theoretical points of view.

Silver(I) complexes with amino acid and dipeptide ligands - Chemical and antimicrobial relevant comparison (mini review).

Diseases caused by various microorganisms accompany humans (as well as animals) throughout their whole lives. After germs penetration to the body, the incubation period and infection developing, an infection can cause mild or severe symptoms, not infrequently even death. The immune system naturally defends itself against pathogens with various mechanisms. One of them is the synthesis of antimicrobial peptides. In the case of serious and severe infections, it is currently possible to help the natural immunity by administration of antimicrobial drugs (AMB) with good success since their discovery at the beginning of the last century. However, their excessive use leads to the development of pathogenic microorganisms' resistance to AMB drugs. Based on this, it is necessary to constantly develop new classes of AMB drugs that will be effective against pathogens, even resistant ones. The field of bioinorganic chemistry, similarly to other biological, chemical, or pharmaceutical sciences, discovers various options and approaches for antimicrobial treatment, from the development of new drugs to drug delivery systems. One of the approaches is the design and preparation of potential drugs based on metal ions and antimicrobial peptides. Various metal ions and amino acid or peptide ligands are used for this purpose. In this mini review, we focused on a reliable comparison of the chemical structure and biological properties of selected silver(I) complexes based on amino acids and dipeptides.

Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity.

The synthesis, anticancer, and antioxidant activities of a series of indole-derived hybrid chalcones are reported here. First, using the well-known Claisen-Schmidt condensation method, a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on five cancer cell lines (HCT116, HeLa, Jurkat, MDA-MB-231, and MCF7) and two non-cancer cell lines (MCF-10A and Bj-5ta). Chalcone 18c, bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using three different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals as well as the FRAP method demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy-substituted chalcones 19a-c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and antiproliferative activity.

Derivatives Incorporating Acridine, Pyrrole, and Thiazolidine Rings as Promising Antitumor Agents.

Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC50 values below 10 µM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines.

Ga(III) pyridinecarboxylate complexes: potential analogues of the second generation of therapeutic Ga(III) complexes?

A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)3]·H2O (GaPic; HPic = picolinic acid), H3O[Ga(Dpic)2]·H2O (GaDpic; H2Dpic = dipicolinic acid), [Ga(Chel)(H2O)(OH)]2·4H2O (GaChel; H2Chel = chelidamic acid) and [Ga(Cldpic)(H2O)(OH)]2 (GaCldpic; H2Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H2Dpic systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)2]+ (logß021 = 16.23(6)), [Ga(Pic)3] (logß031 = 20.86(2)), [Ga(Dpic)2]- (logß021 = 15.42(9)) and [Ga(Dpic)2(OH)]2- (logß-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC50 (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 µM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.

Low-dimensional compounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) complex with 8-hydroxyquinoline-2-carboxylic acid.

A new zirconium(IV) complex, diaquabis(8-hydroxyquinoline-2-carboxylato-κ3N,O2,O8)zirconium(IV) dimethylformamide disolvate, [Zr(C10H5NO3)2(H2O)2]·2C3H7NO or [Zr(QCa)2(H2O)2]·2DMF (1) (HQCaH is 8-hydroxyquinoline-2-carboxylic acid and DMF is dimethylformamide), was prepared and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray structure analysis. Complex 1 is a mononuclear complex in which the ZrIV atoms sit on the twofold axis and they are octacoordinated by two N and six O atoms of two tridentate anionic QCa2- ligands, and two aqua ligands. Outside the coordination sphere are two DMF molecules bound to the complex unit by hydrogen bonds. The structure and stability of complex 1 in dimethyl sulfoxide were verified by NMR spectroscopy. The cytotoxic properties of 1 and HQCaH were studied in vitro against eight cancer cell lines, and their selectivity was tested on the BJ-5ta noncancerous cell line. Both the complex and HQCaH exhibited low activity, with IC50 > 200 µM. DNA and human serum albumin (HSA) binding studies showed that 1 binds to calf thymus (CT) DNA via intercalation and is able to bind to the tryptophan binding site of HSA (Trp-214).

Silver(I) pyrrole- and furan-2-carboxylate complexes - From their design and characterization to antimicrobial, anticancer activity, lipophilicity and SAR.

Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2- carboxylic acid, were synthesized and their composition was confirmed using elemental, spectral, thermal and structural analyses. The {[Ag(Py2c)]}n (AgPy2c, Py2c = pyrrole-2-carboxylate) and {[Ag(Fu2c)]}n (AgFu2c, Fu2c = furan-2-carboxylate) solubility and stability in biological test stock solution were confirmed by 1H NMR spectroscopy. The X-ray analysis has enabled us to determine typical argentophilic interactions and bridging carboxylate coordination mode of both ligands. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constant of only one species, i.e., the ML (M = Ag+, L = Fu2c-), log ßML = 0.59 ± 0.04. Antimicrobial and anticancer tests were performed against selected microorganisms and cell lines with new silver(I) complexes and compared with AgSD (silver(I) sulfadiazine) and cisplatin. From their microbial toxicity point of view, selectivity was determined against lactobacilli (AgPy2c is 8× more effective against S. aureus and E. coli and AgFu2c is 8× more effective against E. coli and 4× against S. aureus). AgFu2c significant anticancer activity was determined against Jurkat cell lines (IC50 = 8.00 µM) and was similar to cisPt (IC50 = 6.3 µM) similarly to its selectivity (SI (AgFu2c) = 7.3, SI (cisPt) = 6.4, SI = selectivity index). In addition, cell cycle arrest was observed already in the Sub-G0 phase during a flow cytometry experiment. To evaluate the AgPy2c and AgFu2c bioavailability we also discuss their Lipinski's Rule of Five.

Chalcone-Acridine Hybrid Suppresses Melanoma Cell Progression via G2/M Cell Cycle Arrest, DNA Damage, Apoptosis, and Modulation of MAP Kinases Activity.

This study was focused on investigating the antiproliferative effects of chalcone hybrids in melanoma cancer cells. Among seven chalcone hybrids, the chalcone-acridine hybrid 1C was the most potent and was selected for further antiproliferative mechanism studies. This in vitro study revealed the potent antiproliferative effect of 1C via cell cycle arrest and apoptosis induction. Cell cycle arrest at the G2/M phase was associated with modulation of expression or phosphorylation of specific cell cycle-associated proteins (cyclin B1, p21, and ChK1), tubulins, as well as with the activation of the DNA damage response pathway. Chalcone 1C also induced apoptosis accompanied by mitochondrial dysfunction evidenced by a decrease in mitochondrial membrane potential, increase in Bax/Bcl-xL ratio and cytochrome c release followed by caspase 3/7 activation. In addition, increased phosphorylation of MAP kinases (Erk1/2, p38 and JNK) was observed in chalcone 1C-treated melanoma cells. The strong antiproliferative activities of this chalcone-acridine hybrid suggest that it may be useful as an antimelanoma agent in humans.

Usnic Acid Isolated from Usnea antarctica (Du Rietz) Reduced In Vitro Angiogenesis in VEGF- and bFGF-Stimulated HUVECs and Ex Ovo in Quail Chorioallantoic Membrane (CAM) Assay.

Natural products include a diverse set of compounds of drug discovery that are currently being actively used to target tumor angiogenesis. In the present study, we evaluated the anti-angiogenic activities of secondary metabolite usnic acid isolated from Usena antarctica. We investigated the in vitro effects on proliferation, migration, and tube formation of VEGF- and bFGF-stimulated HUVECs. Ex ovo anti-angiogenic activity was evaluated using the CAM assay. Our findings demonstrated that usnic acid in the concentration of 33.57 µM inhibited VEGF (25 ng/mL) and bFGF (30 ng/mL)-induced HUVECs proliferation, migration, and tube formation. The ex ovo CAM model was used to confirm the results obtained from in vitro studies. VEGF- and bFGF-induced vessel formation was inhibited by usnic acid after 72 h in over 2-fold higher concentrations compared to in vitro. Subsequently, histological sections of affected chorioallantoic membranes were stained with hematoxylin-eosin and alcian blue to determine the number and diameter of vessels as well as the thickness of the individual CAM layers (ectoderm, mesoderm, endoderm). Usnic acid was able to suppress the formation of VEGF- and bFGF-induced vessels with a diameter of less than 100 µm, which was demonstrated by the reduction of mesoderm thickness as well.

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties.

A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA­ctDNA and human serum albumin­HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.

A Comparative Study of Isolated Secondary Metabolites from Lichens and Their Antioxidative Properties.

Free radicals play a critical role in the chemical processes that occur in all cells. Pharmaceutical companies manufacture a variety of synthetically prepared antioxidants, but it is known that many of these can be carcinogenic. As a result, efforts are being made to find natural antioxidants that do not have these side effects. Lichens may be suitable candidates because they contain secondary metabolites with proven antioxidant properties. This could be explained by the presence of compounds with phenolic groups in lichens. The radical scavenging reaction is a chemical reaction governed by stoichiometry, and our aim is to determine the efficacy of these reactions. The aim of this study is to compare metabolite activity based on the same amount of substance involved in radical scavenging, calculated in micromoles rather than weight concentration. This provides an accurate way of comparing radical scavenging activity. We tested superoxide anion scavenging activity and free radical scavenging activity of isolated lichen secondary metabolites and their mixtures in different ratios. The following compounds were isolated and tested for antioxidant activity: gyrophoric acid (Umbilicaria hirsuta), evernic acid (Evernia prunastri), physodic acid, 3-hydroxyphysodic acid, physodalic acid and atranorin (Hypogymnia physodes), and usnic acid (as a synthetic compound). Of all the tested compounds, 3-hydroxyphysodic acid, as well as mixtures containing this metabolite, showed the strongest scavenging activity. The results also demonstrated that calculation by amount of substance leads to a new consideration of antioxidant activity.

Low-dimensional compounds containing bioactive ligands. Part XVII: Synthesis, structural, spectral and biological properties of hybrid organic-inorganic complexes based on [PdCl4]2- with derivatives of 8-hydroxyquinolinium.

In this study, four hybrid organic-inorganic compounds (8-H2Q)2[PdCl4] (1), (H2ClQ)2[PdCl4] (2), (H2NQ)2[PdCl4] (3) and (H2MeQ)2[PdCl4]·2H2O (4) (where 8-H2Q = 8-hydroxyquinolinium, H2ClQ = 5-chloro-8-hydroxyquinolinium, H2NQ = 5-nitro-8-hydroxyquinolinium and H2MeQ = 2-methyl-8-hydroxyquinolinium) were synthesized through organic cation modulation. Single-crystal X-ray structure analysis of compounds 1 and 3 indicates that their structures are planar and consist of [PdCl4]2- anions and 8-H2Q or H2NQ cations, respectively. Both ionic components are held together through ionic interactions and hydrogen bonds forming infinite chains linked through π-π interactions to form 2D structures. Furthermore, NMR spectroscopy, UV-Vis spectroscopy, elemental analysis, and FT-IR spectroscopy were used to explore the synthesized compounds. The DNA interaction, antimicrobial activity, antiproliferative activity, and radical scavenging effect of the compounds were evaluated. The hybrid compounds and their free ligands can interact with the calf thymus DNA via an intercalation mode involving the insertion of the aromatic chromophore between the base pairs of DNA; compound 1 has the highest binding affinity. Moreover, they have high antimicrobial efficacy against the tested 14 strains of microorganisms with minimum inhibitory concentration values ranging from <1.95 to 250 µg/mL. The antiproliferative activity of the compounds was investigated against three different cancer cell lines, and their selectivity was verified on mesenchymal stem cells. Compounds 1 and 2 displayed selective and high cytotoxicity against human lung and breast cancer cells and showed moderate cytotoxicity against colon cancer cells. Accordingly, they might be auspicious candidates for future pharmacological investigations in lung and breast cancer research.

Antimicrobial and Anticancer Application of Silver(I) Dipeptide Complexes.

Three silver(I) dipeptide complexes [Ag(GlyGly)]n(NO3)n (AgGlyGly), [Ag2(GlyAla)(NO3)2]n (AgGlyAla) and [Ag2(HGlyAsp)(NO3)]n (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 µM.

Potential Effect of Pseudevernia furfuracea (L.) Zopf Extract and Metabolite Physodic Acid on Tumour Microenvironment Modulation in MCF-10A Cells.

Lichens comprise a number of unique secondary metabolites with remarkable biological activities and have become an interesting research topic for cancer therapy. However, only a few of these metabolites have been assessed for their effectiveness against various in vitro models. Therefore, the aim of the present study was to assess the effect of extract Pseudevernia furfuracea (L.) Zopf (PSE) and its metabolite physodic acid (Phy) on tumour microenvironment (TME) modulation, focusing on epithelial-mesenchymal transition (EMT), cancer-associated fibroblasts (CAFs) transformation and angiogenesis. Here, we demonstrate, by using flow cytometry, Western blot and immunofluorescence microscopy, that tested compounds inhibited the EMT process in MCF-10A breast cells through decreasing the level of different mesenchymal markers in a time- and dose-dependent manner. By the same mechanisms, PSE and Phy suppressed the function of Transforming growth factor beta (TGF-ß)-stimulated fibroblasts. Moreover, PSE and Phy resulted in a decreasing level of the TGF-ß canonical pathway Smad2/3, which is essential for tumour growth. Furthermore, PSE and Phy inhibited angiogenesis ex ovo in a quail embryo chorioallantoic model, which indicates their potential anti-angiogenic activity. These results also provided the first evidence of the modulation of TME by these substances.

Zinc(ii) and cadmium(ii) amorphous metal-organic frameworks (aMOFs): study of activation process and high-pressure adsorption of greenhouse gases.

Two novel amorphous metal-organic frameworks (aMOFs) with chemical composition {[Zn2(MTA)]·4H2O·3DMF} n (UPJS-13) and {[Cd2(MTA)]·5H2O·4DMF} n (UPJS-14) built from Zn(ii) and Cd(ii) ions and extended tetrahedral tetraazo-tetracarboxylic acid (H4MTA) as a linker were prepared and characterised. Nitrogen adsorption measurements were performed on as-synthesized (AS), ethanol exchanged (EX) and freeze-dried (FD) materials at different activation temperatures of 60, 80, 100, 120, 150 and 200 °C to obtain the best textural properties. The largest surface areas of 830 m2 g-1 for UPJS-13 (FD) and 1057 m2 g-1 for UPJS-14 (FD) were calculated from the nitrogen adsorption isotherms for freeze-dried materials activated at mild activation temperature (80 °C). Subsequently, the prepared compounds were tested as adsorbents of greenhouse gases, carbon dioxide and methane, measured at high pressures. The maximal adsorption capacities were 30.01 wt% CO2 and 4.84 wt% CH4 for UPJS-13 (FD) and 24.56 wt% CO2 and 6.38 wt% CH4 for UPJS-14 (FD) at 20 bar and 30 °C.

An in vitro selective inhibitory effect of silver(i) aminoacidates against bacteria and intestinal cell lines and elucidation of the mechanism of action by means of DNA binding properties, DNA cleavage and cell cycle arrest.

Novel silver(i) aminoacidate complexes {[Ag(HVal)(H2O)(NO3)]}n (AgVal) and {[Ag3(HAsp)2(NO3)]}n·nH2O (AgAsp) were prepared, investigated and fully characterized by vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis, X-ray crystallography and mass spectrometry. Their stability in D2O and PBS buffer was verified by time-dependent 1H and 13C NMR measurements. Their in vitro antibacterial activity (against pathogenic Staphylococcus aureus CCM4223, Escherichia coli CCM4787) and that against probiotic bacteria Lactobacillus plantarum CCM7102 and Lactobacillus reuteri (L26) were determined and potential dosing concentration was evaluated. The cytotoxicity of both the complexes against intestinal porcine epithelial (IPEC-1) and human epithelial colorectal adenocarcinoma (CaCo-2) cell lines was determined using the colorimetric MTT assay and against human metastatic melanoma (A2058), human pancreatic adenocarcinoma (PaTu 8902), human cervical adenocarcinoma (HeLa), human colorectal carcinoma (HCT116), human leukaemic T cell lymphoma (Jurkat), and human dermal fibroblasts (HDF) using colorimetric MTS assay. The selectivity index (SI) was identified for intestinal cancer (CaCo-2) and healthy (IPEC-1) cells. The mechanism of action of AgVal and AgAsp was further elucidated and discussed by the study of their binding affinity toward the CT DNA, the ability to cleave the supercoiled form of pUC19 DNA and the ability to influence numbers of cells within each cell cycle.

Ethylene Induction of Non-Enzymatic Metabolic Antioxidants in Matricaria chamomilla.

Phytochemical investigations of Matricaria chamomilla L. (Asteraceae) stated the presence of several compounds with an established therapeutic and antioxidant potential. The chamomile non-enzymatic antioxidant system includes low molecular mass compounds, mainly polyphenols such as cinnamic, hydroxybenzoic and chlorogenic acids, flavonoids and coumarins. The objective of this work was to evaluate the role of the non-enzymatic antioxidant system after stimulation by ethylene in tetraploid chamomile plants. Seven days of ethylene treatment significantly increased the activity of phenylalanine ammonia-lyase, which influenced the biosynthesis of protective polyphenols in the first step of their biosynthetic pathway. Subsequently, considerable enhanced levels of phenolic metabolites with a substantial antioxidant effect (syringic, vanillic and caffeic acid, 1,5-dicaffeoylquinic acid, quercetin, luteolin, daphnin, and herniarin) were determined by HPLC-DAD-MS. The minimal information on the chlorogenic acids function in chamomile led to the isolation and identification of 5-O-feruloylquinic acid. It is accumulated during normal conditions, but after the excessive effect of abiotic stress, its level significantly decreases and levels of other caffeoylquinic acids enhance. Our results suggest that ethephon may act as a stimulant of the production of pharmaceutically important non-enzymatic antioxidants in chamomile leaves and thus, lead to an overall change in phytochemical content and therapeutic effects of chamomile plants, as well.

In vitro biological evaluation and consideration about structure-activity relationship of silver(I) aminoacidate complexes.

Two silver(I) aminoacidate complexes {[Ag4(L-HAla)4(NO3)3]NO3}n (AgAla, complex 1, Ala = alanine) and {[Ag(L-Phe)]}n (AgPhe, complex 2, Phe = phenylalanine) were prepared and characterized by elemental, spectral analysis (FT-IR, NMR techniques) and single crystal X-ray analysis in solid state and their solution stability was measured in biological testing time-scale by 1H NMR. The bridging coordination modes of the zwitterionic Ala and deprotonated Phe ligands led to the formation of 1D polymeric chains of the complexes. The significant argentophilic interactions are presented in the structure of AgAla. Antimicrobial testing of prepared Ag(I) complexes was evaluated by IC50 and MIC values and were compared with AgGly, silver(I) sulfadiazine and AgNO3 samples. Moreover, MTS test was used to the testing of broad range antiproliferative activity of studied compounds against different cancer cell lines and also to the investigation of calf thymus DNA interactions by absorption spectroscopy, fluorescence spectroscopy, Ethidium bromide/Hoechst 33258 displacement experiments and circular dichroism spectroscopy. To evaluate the pUC19 DNA fragmentation by silver(I) complexes, the agarose gel electrophoresis was used. In addition to biological evaluation we used lipophilicity measurement results in the discussion about structure-activity relationship (SAR).

Synthesis and mannosidase inhibitory profile of a small library of aminocyclitols from shikimic acid-derived scaffolds.

A short synthetic route to a small library of aminocyclitols 14·HCl-19·HCl has been elaborated from the common shikimic acid-derived scaffolds 20 and 21. The developed strategy features three oxidative processes ‒ ozonolysis, dihydroxylation and epoxidation ‒ as the key transformations. The stereochemistry of the newly created stereocentres was confirmed either via crystallographic analysis or by means of NOESY experiments conducted on advanced intermediates. Glycosidase inhibition study revealed no glucosidase inhibition and only weak inhibitory activity against recombinant Drosophila melanogaster Golgi mannosidase (GMIIb).