Critical view on antimicrobial, antibiofilm and cytotoxic activities of quinazolin-4(3H)-one derived schiff bases and their Cu(II) complexes.

A series of nine 2,3-disubstituted-quinazolin-4(3H)-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084. While anti-enterococcal and antimycobacterial activities were insignificant, 3-[(E)-(2-hydroxy-5-nitrobenzylidene)amino]-2-(2-hydroxy-5-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (SB3) and its Cu(II) complex (SB3-Cu) demonstrated bacteriostatic antistaphylococcal activity. In addition, both compounds, as well as the other two prepared complexes, showed antibiofilm activity, which resulted in a reduction of biofilm formation and eradication of mature S. aureus biofilm by 80% even at concentrations lower than the values of their minimum inhibitory concentrations. In addition, the compounds were tested for their cytotoxic effect on the human monocytic leukemia cell line THP-1. The antileukemic efficiency was improved by the preparation of Cu(II) complexes from the corresponding non-chelated Schiff base ligands.

New Unnatural Gallotannins: A Way toward Green Antioxidants, Antimicrobials and Antibiofilm Agents.

Nature has been a source of inspiration for the development of new pharmaceutically active agents. A series of new unnatural gallotannins (GTs), derived from d-lyxose, d-ribose, l-rhamnose, d-mannose, and d-fructose have been designed and synthesized in order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. The structures of the new compounds were confirmed by various spectroscopic methods. Apart from spectral analysis, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and iron reducing power (FRAP) assays. Antibacterial activity of compounds was tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. For screening of antimycobacterial effect, a virulent isolate of Mycobacterium tuberculosis and two non-tuberculous mycobacteria were used. Furthermore, antibiofilm activity of structurally different GTs against S. aureus, and their ability to inhibit sortase A, were inspected. Experimental data revealed that the studied GTs are excellent antioxidants and radical-scavenging agents. The compounds exhibited only a moderate antibacterial effect against Gram-positive pathogens S. aureus and E. faecalis and were practically inactive against mycobacteria. However, they were efficient inhibitors and disruptors of S. aureus biofilms in sub-MIC concentrations, and interacted with the quorum-sensing system in Chromobacteriumviolaceum. Overall, these findings suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, consumer products, and for food industry applications.

Evaluation of surface active and antimicrobial properties of alkyl D-lyxosides and alkyl L-rhamnosides as green surfactants.

The use of carbohydrates, as a part of surface-active compounds, has been studied due to their biodegradability and nontoxic profile. A series of alkyl glycosides containing d-lyxose and l-rhamnose with alkyl chains of 8-12 carbon atoms were investigated. The effects of structural variations on their physico-chemical and biological properties have been evaluated for a detailed understanding of their properties. Alkyl glycosides were tested on their toxicity against bacterial cells of the genus Pseudomonas (MTT assay), microbiological adhesion to hydrocarbons (MATH assay), cell surface hydrophobicity (Congo red assay), cell membrane permeability (crystal violet assay), and bacterial biofilm formation. Furthermore, their antifungal activity against two pathogenic microorganisms Candida albicans and Aspergillus niger was investigated using the disc diffusion method. Toxicological studies revealed that compounds could reduce the metabolic activity of bacterial cells only moderately but they increased the hydrophobicity of cell surface in Pseudomonas strains. In addition, alkyl glycosides changed the permeability of the cell membranes to the level of 30-40% for this strain. The compounds with an even number of carbon atoms in their alkyl chain promoted stronger bacterial biofilm formation on the glass surface. All studied derivatives demonstrated very strong antifungal activity against fungus A. niger but very small effect against C. albicans. Overall, the results showed that long-chain alkyl glycosides could be considered as inexpensive, biocompatible, nontoxic agents, and serve for the surface design to avoid bacterial adhesion as an alternative solution to antibiotic treatment.

Antioxidant, Cytotoxic, Genotoxic, and DNA-Protective Potential of 2,3-Substituted Quinazolinones: Structure-Activity Relationship Study.

The evaluation of antioxidant compounds that counteract the mutagenic effects caused by the direct action of reactive oxygen species on DNA molecule is of considerable interest. Therefore, a series of 2,3-substituted quinazolinone derivatives (Q1-Q8) were investigated by different assays, and the relationship between their biological properties and chemical structure was examined. Genotoxicity and the potential DNA-protective effects of Q1-Q8 were evaluated by comet assay and DNA topology assay. Antioxidant activity was examined by DPPH-radical-scavenging, reducing-power, and total antioxidant status (TAS) assays. The cytotoxic effect of compounds was assessed in human renal epithelial cells (TH-1) and renal carcinoma cells (Caki-1) by MTT assay. Analysis of the structure-activity relationship disclosed significant differences in the activity depending on the substitution pattern. Derivatives Q5-Q8, bearing electron-donating moieties, were the most potent members of this series. Compounds were not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants (H2O2, Fe2+ ions). Furthermore, compounds exhibited higher cytotoxicity in Caki-1 compared to that in TH-1 cells. Substantial antioxidant effect and DNA-protectivity along with the absence of genotoxicity suggested that the studied quinazolinones might represent potential model structures for the development of pharmacologically active agents.

Evaluation of the genotoxic, DNA-protective and antioxidant profile of synthetic alkyl gallates and gallotannins using in vitro assays.

New gallotanins, methyl 2,3,4,6-tetra-O-galloyl-α-D-glucoside (G4Glc), methyl 2,3,4,6-tetra-O-galloyl-α-D-mannoside (G4Man), and methyl 2,3,4-tri-O-galloyl-α-L-rhamnoside (G3Rham), have been synthesized in order to study the protective effects of synthetic polyphenols that are structurally related with natural compounds. Apart from spectral analysis, examination of antioxidant ability and protective efficiency showed the differences among newly prepared compounds and commercial antioxidants - gallic acid (GA), methyl gallate (MG), and octyl gallate (OG) applying radical scavenging 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and iron-chelating assays. The genotoxicity and DNA-protective potential of tested compounds on human peripheral blood mononuclear cells (PBMCs) were evaluated using the single-cell gel electrophoresis (comet assay) and DNA-topology assay. Experimental data revealed that gallotannins G3Rham, G4Man, and G4Glc possess significant radical scavenging/antioxidant activities and manifest very low genotoxic effect on human PBMCs. Moreover, tested compounds considerably reduce the level of DNA damage induced by hydrogen peroxide or Fe2+-ions. The results imply that new synthetic gallotannins can be considered as nontoxic agents for subsequent design of new antioxidants with potential biomedical applications.

Alkyl Xylosides: Physico-Chemical Properties and Influence on Environmental Bacteria Cells.

A group of four selected non-ionic surfactants based on carbohydrates, namely octyl d-xyloside (C8X), nonyl d-xyloside (C9X), decyl d-xyloside (C10X) and dodecyl d-xyloside (C12X), have been investigated to accomplish a better understanding of their physico-chemical properties as well as biological activities. The surface-active properties, such as critical micelle concentration (CMC), emulsion and foam stability, the impact of the compounds on cell surface hydrophobicity and cell membrane permeability together with their toxicity on the selected bacterial strains have been determined as well. The studied group of surfactants showed high surface-active properties allowing a decrease in the surface tension to values below 25 mN m-1 for dodecyl d-xyloside at the CMC. The investigated compounds did not have any toxic influence on two Pseudomonas bacterial strains at concentrations below 25 mg L-1. The studied long-chain alkyl xylosides influenced both the cell inner membrane permeability and the cell surface hydrophobicity. Furthermore, the alkyl chain length, as well as the surfactant concentration, had a significant impact on the modifications of the cell surface properties. The tested non-ionic surfactants exhibited strong surface-active properties accompanied by the significant influence on growth and properties of Pseudomonas bacteria cells.

Surfactants of biological origin: The role of Mo(VI) and microwaves in the synthesis of xylan-based non-ionic surfactants.

Microwave-assisted, phosphomolybdic acid (PMoA) catalyzed, glycosylation of unprotected d-xylose and d-lyxose, obtained after tandem Mo(VI)-catalyzed xylan hydrolysis-epimerization reaction, provides alkyl xylosides and lyxosides in short reaction times. A homologous series of amphiphilic alkyl pentosides varying in chain structure (C8-C14) was prepared in very good yields (38-73%). A new catalytic approach using the reusable heterogeneous PMoA/SiO2 catalyst provides benefits in terms of yields, environmental safety, operational simplicity, and thus opens new perspectives for the rational hemicellulose biomass utilization.

Xylans are a valuable alternative resource: production of D-xylose, D-lyxose and furfural under microwave irradiation.

The influence of microwave irradiation on hydrolysis of xylan and simultaneous epimerization of the D-xylose to D-lyxose has been studied. An acidic solution of xylan was treated with catalytic amount of sodium molybdate and the composition of the reaction mixture was analyzed. Short reaction times of hydrolysis and subsequent epimerization reaction provided an equilibrium reaction mixture of D-xylose and D-lyxose (1.6:1) without significant formation of undesirable side products. Obtained pentoses can be reduced to the corresponding alditols (D-xylitol and D-lyxitol) in very good yields (88% and 85%) or can be further dehydrated to furfural (53%). Combined use of Mo(VI) catalyst and microwave irradiation allows better conversions and substantial reduction of reaction times (400-fold) compared to that obtained by conventional heating. Studied stereospecific transformation of xylan proceeds with high selectivity, short reaction times and very good yields that makes this approach attractive also for preparative purposes.

A new type of rearrangement in branched-chain carbohydrates: isomerization of 3-C-branched aldoses.

A new type of rearrangement is described for 3-C-branched chain aldoses. The studied transformation is based on the Mo(VI)-catalyzed isomerization of carbohydrate carbon skeleton and allows preparation of C-3 isomers of 3-C-branched aldoses in a simple way without formation of side products. This rearrangement at C-3 carbon differs from the previously described epimerization at C-2 of aldoses catalyzed by Mo(VI) ions, known as Bílik reaction. The potential of this new transformation is illustrated on the preparation of new, 3-C-methyl-D-glucose and 3-C-vinyl-D-glucose from 3-C-methyl-d-allose and 3-C-vinyl-D-allose, respectively.

The effect of microwave irradiation on Mo(VI) catalyzed transformations of reducing saccharides.

Efficient microwave-assisted Mo(VI)-catalyzed transformations of the 10 most common aldoses are described. Both pentoses and hexoses were converted to the corresponding epimers in considerably shorter reaction times. The yields were comparable, or better compared to conventional synthetic methods.

NMR studies of molybdate complexes of D-erythro-L-manno-octose and D-erythro-L-gluco-octose and their alditols.

Different amounts and various types of bis-dinuclear tetradentate molybdate complexes of D-erythro-L-manno-octose, D-erythro-L-gluco-octose, D-erythro-L-manno-octitol and D-erythro-L-gluco-octitol were characterized by 1H and 13C NMR spectroscopy in aqueous solutions. Detailed analysis of 1H-(1)H coupling constants and NOEs, together with chemical shifts, allowed characterization of the different isomers of these complexes.