Elicitins are proteinaceous elicitors that induce the hypersensitive response and plant resistance against diverse phytopathogens. Elicitin recognition by membrane receptors or high-affinity sites activates a variety of fast responses including the production of reactive oxygen species (ROS) and nitric oxide (NO), leading to induction of plant defense genes. Beta-cryptogein (CRY) is a basic β-elicitin secreted by the oomycete Phytophthora cryptogea that shows high necrotic activity in some plant species, whereas infestin 1 (INF1) secreted by the oomycete P. infestans belongs to acidic α-elicitins with a significantly weaker capacity to induce necrosis. We compared several mutated forms of β-CRY and INF1 with a modulated capacity to trigger ROS and NO production, bind plant sterols and induce cell death responses in cell cultures of Nicotiana tabacum L. cv. Xanthi. We evidenced a key role of the lysine residue in position 13 in basic elicitins for their biological activity and enhancement of necrotic effects of acidic INF1 by the replacement of the valine residue in position 84 by larger phenylalanine. Studied elicitins activated in differing intensity signaling pathways of ROS, NO and phytohormones jasmonic acid, ethylene and salicylic acid, known to be involved in triggering of hypersensitive response and establishment of systemic resistance.

• Keywords
• Cryptogein, Elicitins, Infestin, Nitric oxide, Plant defense responses, Reactive oxygen species,
• MeSH
• Algal Proteins genetics   MeSH
• Nitrogen * MeSH
• Fungal Proteins metabolism   MeSH
• Oxygen MeSH
• Phytophthora * MeSH
• Reactive Oxygen Species MeSH
• Plants metabolism   MeSH
• Amino Acid Sequence MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Algal Proteins MeSH
• Nitrogen * MeSH
• Fungal Proteins MeSH
• Oxygen MeSH
• Reactive Oxygen Species MeSH

The formation and detailed spectroscopic characterization of the first biuret-containing monoanionic superoxido-NiII intermediate [LNiO2 ]- as the Li salt [2; L=MeN[C(=O)NAr)2 ; Ar=2,6-iPr2 C6 H3 )] is reported. It results from oxidation of the corresponding [Li(thf)3 ]2 [LNiII Br2 ] complex M with excess H2 O2 in the presence of Et3 N. The [LNiO2 ]- core of 2 shows an unprecedented nucleophilic reactivity in the oxidative deformylation of aldehydes, in stark contrast to the electrophilic character of the previously reported neutral Nacnac-containing superoxido-NiII complex 1, [L'NiO2 ] (L'=CH(CMeNAr)2 ). According to density-functional theory (DFT) calculations, the remarkably different behaviour of 1 versus 2 can be attributed to their different charges and a two-state reactivity, in which a doublet ground state and a nearby spin-polarized doublet excited-state both contribute in 1 but not in 2. The unexpected nucleophilicity of the superoxido-NiII core of 2 suggests that such a reactivity may also play a role in catalytic cycles of Ni-containing oxygenases and oxidases.

• Keywords
• dioxygen ligands, nickel, structure elucidation, structure-activity relationships, two-state reactivity,
• MeSH
• Coordination Complexes chemistry   MeSH
• Quantum Theory MeSH
• Oxygen chemistry   MeSH
• Lithium chemistry   MeSH
• Models, Molecular MeSH
• Nickel chemistry   MeSH
• Oxidation-Reduction MeSH
• Oxidoreductases chemistry   MeSH
• Oxygenases chemistry   MeSH
• Salts chemistry   MeSH
• Superoxides chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Names of Substances
• Coordination Complexes MeSH
• Oxygen MeSH
• Lithium MeSH
• Nickel MeSH
• Oxidoreductases MeSH
• Oxygenases MeSH
• Salts MeSH
• Superoxides MeSH

A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.

• Keywords
• BSA oxidation, Cytotoxic activity, Cytotoxicity of O-Mesylates, DFT calculations, Oxidation of triterpenoids, SeO(2) oxidation, α-phenylseleno-ketone,
• MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Oxidation-Reduction MeSH
• Pentacyclic Triterpenes MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Drug Screening Assays, Antitumor MeSH
• Selenium * chemistry   MeSH
• Density Functional Theory MeSH
• Triterpenes * chemistry   pharmacology   chemical synthesis   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• lupane MeSH Browser
• Pentacyclic Triterpenes MeSH
• Antineoplastic Agents * MeSH
• Selenium * MeSH
• Triterpenes * MeSH

Systematic structure-activity studies on a diverse family of nucleoside phosphonic acids has led to the development of potent antiviral drugs such as HPMPC (CidofovirTM), PMEA (AdefovirTM), and PMPA (TenofovirTM), which are used in the treatment of CMV-induced retinitis, hepatitis B, and HIV, respectively. Here, we present the synthesis of a novel class of acyclic phosphonate nucleotides that have a locked conformation via a pyrrolidine ring. NMR analysis of these compounds revealed that the pyrrolidine ring has a constrained conformation when in the cis-form at pD < 10 via hydrogen bonding. Four of these compounds were tested as inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases. The most potent has a Ki of 0.6 μM for Plasmodium falciparum HGXPRT.

• MeSH
• Adenine chemistry   MeSH
• Antimalarials chemical synthesis   MeSH
• Chemistry, Pharmaceutical MeSH
• Hypoxanthine chemistry   MeSH
• Kinetics MeSH
• Hydrogen-Ion Concentration MeSH
• Protein Conformation MeSH
• Oxygen chemistry   MeSH
• Humans MeSH
• Magnetic Resonance Spectroscopy MeSH
• Organophosphonates chemistry   MeSH
• Pentosyltransferases antagonists & inhibitors   MeSH
• Plasmodium falciparum drug effects   MeSH
• Pyrrolidines chemistry   MeSH
• Drug Design MeSH
• Hydrogen Bonding MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenine MeSH
• Antimalarials MeSH
• Hypoxanthine MeSH
• Oxygen MeSH
• Organophosphonates MeSH
• Pentosyltransferases MeSH
• purine phosphoribosyltransferase MeSH Browser
• Pyrrolidines MeSH

The differential rate of synthesis of penicillinamidohydrolase (penicillin acylase -- EC 3.5.1.11) was studied in Escherichia coli growing in some chemically defined media and in a complex medium. The enzyme is synthesized at a constant rate only during the exponential phase of growth of cells. Its synthesis is induced most effectively (with respect to quantity) by phenylacetic acid. The induction lag of the enzyme synthesis in a medium with acetate corresponds to two generation times. The highest rate of the enzyme synthesis is reached in a medium containing phenylacetic acid as the only source of carbon and energy. The enzyme synthesis is fully repressed by an increased concentration of dissolved oxygen in the medium, even when Escherichia coli is cultivated in the medium with phenylacetic acid as the only carbon and energy source.

• MeSH
• Amidohydrolases biosynthesis   MeSH
• Amides pharmacology   MeSH
• Enzyme Induction MeSH
• Enzyme Repression MeSH
• Escherichia coli enzymology   growth & development   MeSH
• Phenoxyacetates pharmacology   MeSH
• Phenylacetates pharmacology   MeSH
• Kinetics MeSH
• Culture Media MeSH
• Oxygen pharmacology   MeSH
• Penicillin Amidase biosynthesis   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amidohydrolases MeSH
• Amides MeSH
• Phenoxyacetates MeSH
• Phenylacetates MeSH
• Culture Media MeSH
• Oxygen MeSH
• Penicillin Amidase MeSH

Polyethylene was implanted with 30-keV oxygen (PE/O+) or 23-keV carbon ions (PE/C+) at 10(13) to 5 x 10(15) ions cm(-2) doses in order to improve the adhesion of vascular smooth muscle cell (VSMC) to the polymer surface in vitro because of its oxidation and carbon-enrichment. The concentration of -CO- groups in the PE/O+ and PE/C+ samples increased only up to doses of 3 x 10(14) and 10(15) ions cm(-2), respectively, and then declined. At the same time, the concentration of these groups, measured at a dose of 3 x 10(14) ions cm(-2), was higher in PE/O+ than in PE/C+ samples. Similarly, the number of initially-adhering rat VSMC (24 h after seeding) increased only up to a dose of 3 x 10(13) and 10(15) ions cm(-2) on PE/O+ and PE/C+ samples, respectively. In addition, between doses of 10(13) and 10(14) ions cm(-2), this number was about two to three times higher on PE/O+ samples. On the other hand, the surface wettability increased proportionally to the implanted ion dose, especially above a dose of 10(14) ions cm(-2). Thus, the number of initially-adhered cells appeared to be positively correlated with the amount of the oxygen group present at the polymer surface rather than with the surface wettability. The higher cell adhesion was accompanied by adsorption of fluorescent dye-conjugated collagen IV in larger amounts. The highest numbers of initially-adhered cells were usually associated with the lowest rates of subsequent proliferation (measured by the doubling time, BrdU labelling and M

• MeSH
• Biocompatible Materials chemistry   metabolism   pharmacology   MeSH
• Cell Adhesion MeSH
• Cell Division MeSH
• Electrochemistry MeSH
• Cations chemistry   MeSH
• Collagen Type IV pharmacokinetics   MeSH
• Rats MeSH
• Oxygen chemistry   MeSH
• Polyethylenes chemistry   metabolism   pharmacology   MeSH
• Surface Properties MeSH
• Wettability MeSH
• Muscle, Smooth, Vascular cytology   drug effects   MeSH
• Carbon chemistry   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Cations MeSH
• Collagen Type IV MeSH
• Oxygen MeSH
• Polyethylenes MeSH
• Carbon MeSH

Effects of melatonin and some structurally related indole compounds were studied by in vitro methods such as (i) an inhibition of the hyaluronic acid degradation and (ii) a standard lipid peroxidation assay. In vivo approach was based on the alloxan model of hyperglycaemia. Reduction of the viscosity of a hyaluronic acid solution in the reaction mixture was inhibited by tryptamine (91% inhibition), as well as by indole-3-carboxylic acid and indomethacin (80% and 77% inhibition, respectively). Lipid peroxidation with tert-butyl hydroperoxide as a source of radicals was followed by the formation of thiobarbituric acid reactive substances. Tested drugs inhibited lipid peroxidation in the order: tryptamine (59%) > indole-2-carboxylic acid (38%) > indomethacin (26%) > melatonin and indole-3-carboxylic acid (13%). In vivo, alloxan-induced hyperglycaemia was reduced in mice pretreated with drugs tested. The highest protective effect was observed with indomethacin (52% inhibition), followed by tryptamine and melatonin (18% and 16% inhibition, respectively).

• MeSH
• Alloxan MeSH
• Antioxidants pharmacology   MeSH
• Hyperglycemia chemically induced   drug therapy   MeSH
• Indoles chemistry   metabolism   pharmacology   MeSH
• Indomethacin chemistry   metabolism   MeSH
• Liver metabolism   MeSH
• Rats MeSH
• Hyaluronic Acid metabolism   MeSH
• Carboxylic Acids MeSH
• Oxygen chemistry   metabolism   MeSH
• Malondialdehyde analysis   MeSH
• Melatonin chemistry   metabolism   pharmacology   MeSH
• Mitochondria drug effects   metabolism   MeSH
• Lipid Peroxidation drug effects   MeSH
• Rats, Wistar MeSH
• Reference Values MeSH
• In Vitro Techniques MeSH
• Tryptamines chemistry   metabolism   MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Alloxan MeSH
• Antioxidants MeSH
• indole-2-carboxylic acid MeSH Browser
• indole-3-carboxylic acid MeSH Browser
• Indoles MeSH
• Indomethacin MeSH
• Hyaluronic Acid MeSH
• Carboxylic Acids MeSH
• Oxygen MeSH
• Malondialdehyde MeSH
• Melatonin MeSH
• tryptamine MeSH Browser
• Tryptamines MeSH

The function of the antigen-5/CAP family of proteins found in the salivary gland of bloodsucking animals has remained elusive for decades. Antigen-5 members from the hematophagous insects Dipetalogaster maxima (DMAV) and Triatoma infestans (TIAV) were expressed and discovered to attenuate platelet aggregation, ATP secretion, and thromboxane A2 generation by low doses of collagen (<1 μg/ml) but no other agonists. DMAV did not interact with collagen, glycoprotein VI, or integrin α2β1. This inhibitory profile resembles the effects of antioxidants Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in platelet function. Accordingly, DMAV was found to inhibit cytochrome c reduction by O2[Symbol: see text] generated by the xanthine/xanthine oxidase, implying that it exhibits antioxidant activity. Moreover, our results demonstrate that DMAV blunts the luminescence signal of O2[Symbol: see text] generated by phorbol 12-myristate 13-acetate-stimulated neutrophils. Mechanistically, inductively coupled plasma mass spectrometry and fluorescence spectroscopy revealed that DMAV, like Cu,Zn-SOD, interacts with Cu(2+), which provides redox potential for catalytic removal of O2[Symbol: see text]. Notably, surface plasmon resonance experiments (BIAcore) determined that DMAV binds sulfated glycosaminoglycans (e.g. heparin, KD ~100 nmol/liter), as reported for extracellular SOD. Finally, fractions of the salivary gland of D. maxima with native DMAV contain Cu(2+) and display metal-dependent antioxidant properties. Antigen-5/CAP emerges as novel family of Cu(2+)-dependent antioxidant enzymes that inhibit neutrophil oxidative burst and negatively modulate platelet aggregation by a unique salivary mechanism.

• Keywords
• Blood, Hemostasis, Inflammation, Insect, Toxins,
• MeSH
• Platelet Adhesiveness MeSH
• Platelet Aggregation * MeSH
• Antioxidants metabolism   MeSH
• Phylogeny MeSH
• Glycosaminoglycans metabolism   MeSH
• Collagen metabolism   MeSH
• Horses MeSH
• Oxygen metabolism   MeSH
• Humans MeSH
• Copper metabolism   MeSH
• Molecular Sequence Data MeSH
• Neutrophils metabolism   MeSH
• Hydrogen Peroxide analysis   MeSH
• Surface Plasmon Resonance MeSH
• Swine MeSH
• Respiratory Burst * MeSH
• Free Radical Scavengers metabolism   MeSH
• Amino Acid Sequence MeSH
• Sequence Alignment MeSH
• Sulfur chemistry   MeSH
• Cattle MeSH
• Salivary Glands enzymology   MeSH
• Triatoma enzymology   MeSH
• Sharks MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Names of Substances
• Antioxidants MeSH
• Glycosaminoglycans MeSH
• Collagen MeSH
• Oxygen MeSH
• Copper MeSH
• Hydrogen Peroxide MeSH
• Free Radical Scavengers MeSH
• Sulfur MeSH

Methanogens represent the final decomposition step in anaerobic degradation of organic matter, occurring in the digestive tracts of various invertebrates. However, factors determining their community structure and activity in distinct gut sections are still debated. In this study, we focused on the tropical millipede species Archispirostreptus gigas (Diplopoda, Spirostreptidae) and Epibolus pulchripes (Diplopoda, Pachybolidae), which release considerable amounts of methane. We aimed to characterize relationships between physicochemical parameters, methane production rates, and methanogen community structure in the two major gut sections, midgut and hindgut. Microsensor measurements revealed that both sections were strictly anoxic, with reducing conditions prevailing in both millipedes. Hydrogen concentration peaked in the anterior hindgut of E. pulchripes. In both species, the intestinal pH was significantly higher in the hindgut than in the midgut. An accumulation of acetate and formate in the gut indicated bacterial fermentation activities in the digestive tracts of both species. Phylogenetic analysis of 16S rRNA genes showed a prevalence of Methanobrevibacter spp. (Methanobacteriales), accompanied by a small fraction of so-far-unclassified "Methanomethylophilaceae" (Methanomassiliicoccales), in both species, which suggests that methanogenesis is mostly hydrogenotrophic. We conclude that anoxic conditions, negative redox potential, and bacterial production of hydrogen and formate promote gut colonization by methanogens. The higher activities of methanogens in the hindgut are explained by the higher pH of this compartment and their association with ciliates, which are restricted to this compartment and present an additional source of methanogenic substrates. IMPORTANCE Methane (CH4) is the second most important atmospheric greenhouse gas after CO2 and is believed to account for 17% of global warming. Methanogens are a diverse group of archaea and can be found in various anoxic habitats, including digestive tracts of plant-feeding animals. Termites, cockroaches, the larvae of scarab beetles, and millipedes are the only arthropods known to host methanogens and emit large amounts of methane. Millipedes are ranked as the third most important detritivores after termites and earthworms, and they are considered keystone species in many terrestrial ecosystems. Both methane-producing and non-methane-emitting species of millipedes have been observed, but what limits their methanogenic potential is not known. In the present study, we show that physicochemical gut conditions and the distribution of symbiotic ciliates are important factors determining CH4 emission in millipedes. We also found close similarities to other methane-emitting arthropods, which might be associated with their similar plant-feeding habits.

• Keywords
• Methanobrevibacter, Methanomassiliicoccales, digestive tract, methane, methanogenesis, methanogenic community, physicochemical parameters, tropical millipedes,
• MeSH
• Bacteria genetics   metabolism   MeSH
• Arthropods microbiology   MeSH
• Formates metabolism   MeSH
• Phylogeny MeSH
• Gastrointestinal Tract metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Oxygen analysis   MeSH
• Methane metabolism   MeSH
• Oxidation-Reduction MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Gastrointestinal Microbiome * genetics   MeSH
• Hydrogen metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Formates MeSH
• formic acid MeSH Browser
• Oxygen MeSH
• Methane MeSH
• RNA, Ribosomal, 16S MeSH
• Hydrogen MeSH

The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

• MeSH
• Antitubercular Agents chemistry   pharmacology   MeSH
• Heterocyclic Compounds chemistry   MeSH
• Humans MeSH
• Mice MeSH
• Sulfur analysis   MeSH
• Thiadiazoles chemistry   pharmacology   MeSH
• Thiophenes chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Heterocyclic Compounds MeSH
• Sulfur MeSH
• Thiadiazoles MeSH
• Thiophenes MeSH