Brassinosteroids is involved in methane-induced adventitious root formation via inducing cell wall relaxation in marigold.

BACKGROUND: Methane (CH4) and brassinosteroids (BRs) are important signaling molecules involved in a variety of biological processes in plants. RESULTS: Here, marigold (Tagetes erecta L. 'Marvel') was used to investigate the role and relationship between CH4 and BRs during adventitious root (AR) formation. The results showed a dose-dependent effect of CH4 and BRs on rooting, with the greatest biological effects of methane-rich water (MRW, CH4 donor) and 2,4-epibrassinolide (EBL) at 20% and 1 µmol L- 1, respectively. The positive effect of MRW on AR formation was blocked by brassinoazole (Brz, a synthetic inhibitor of EBL), indicating that BRs might be involved in MRW-regulated AR formation. MRW promoted EBL accumulation during rooting by up-regulating the content of campestanol (CN), cathasterone (CT), and castasterone (CS) and the activity of Steroid 5α-reductase (DET2), 22α-hydroxylase (DWF4), and BR-6-oxidase (BR6ox), indicating that CH4 could induce endogenous brassinolide (BR) production during rooting. Further results showed that MRW and EBL significantly down-regulated the content of cellulose, hemicellulose and lignin during rooting and significantly up-regulated the hydrolase activity, i.e. cmcase, xylanase and laccase. In addition, MRW and EBL also significantly promoted the activity of two major cell wall relaxing factors, xyloglucan endotransglucosylase/hydrolase (XTH) and peroxidase, which in turn promoted AR formation. While, Brz inhibited the role of MRW on these substances. CONCLUSIONS: BR might be involved in CH4-promoted AR formation by increasing cell wall relaxation.

Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies.

We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The anti-biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 µg/mL. Compounds also revealed a promising antibiofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico molecular docking studies revealed DHFR and DNA gyrase B as potential anti-bacterial targets and in silico predictions of ADME suggested adequate drug-likeness profiles for the synthetized triarylmethanes.

Solid-phase synthesis of biocompatible N-heterocyclic carbene-Pd catalysts using a sub-monomer approach.

Taking inspiration from the assembly of so-called peptoids (N-alkylglycine oligomers) we present a new synthetic methodology whereby N-heterocyclic carbene (NHC) based Pd ligands were assembled using a sub-monomer approach and loaded with Pd via solid-phase synthesis. This allowed the rapid generation a library of NHC-palladium catalysts that were readily functionalised to allow bioconjugation. These catalysts were able to rapidly activate a caged fluorophore and 'switch-on' an anticancer prodrug in 3D cell culture.

Nitric oxide contributes to methane-induced osmotic stress tolerance in mung bean.

BACKGROUND: Osmotic stress is a major abiotic stress limiting crop production by affecting plant growth and development. Although previous reports discovered that methane (CH4) has a beneficial effect on osmotic stress, the corresponding downstream signal(s) is still elusive. RESULTS: Polyethylene glycol (PEG) treatment progressively stimulated the production of CH4 in germinating mung bean seeds. Exogenous CH4 and sodium nitroprusside (SNP) not only triggered nitric oxide (NO) production in PEG-stressed plants, but also alleviated the inhibition of seed germination. Meanwhile, amylase activity was activated, thus accelerating the formation of reducing sugar and total soluble sugar. Above responses could be impaired by NO scavenger(s), suggesting that CH4-induced stress tolerance was dependent on NO. Subsequent tests showed that CH4 could reestablish redox balance in a NO-dependent fashion. The addition of inhibitors of the nitrate reductase (NR) and NO synthase in mammalian (NOS), suggested that NR and NOS-like protein might be partially involved in CH4-alleviated seed germination inhibition. In vitro and scavenger tests showed that NO-mediated S-nitrosylation might be associated with above CH4 responses. CONCLUSIONS: Together, these results indicated an important role of endogenous NO in CH4-enhanced plant tolerance against osmotic stress, and NO-regulated redox homeostasis and S-nitrosylation might be involved in above CH4 action.

Inhibition of tubulin polymerization by select alkenyldiarylmethanes.

During studies on the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), analogues were discovered that exhibit low micromolar and submicromolar cytotoxicities. Since the ADAMs are structurally related to the tubulin polymerization inhibitor CC-5079, a set of 14 ADAMs were tested for inhibition of tubulin polymerization in an attempt to identify the biological target responsible for their cytotoxicity. The results indicate that, overall, the ADAMs are poor inhibitors of tubulin polymerization. However, the two most cytotoxic compounds, 15 and 16, are in fact active as inhibitors of tubulin assembly with IC(50) values of 3.7+/-0.3 and 2.8+/-0.2 microM, respectively, and they both inhibit the binding of colchicine to tubulin. Both compounds were investigated for anticancer activity in the National Cancer Institute's panel of 60 human cancer cell lines, and both compounds consistently displayed submicromolar cytotoxicities with mean-graph midpoint (MGM) values of 0.31+/-0.08 and 0.47+/-0.09 microM, respectively.

Methane protects against polyethylene glycol-induced osmotic stress in maize by improving sugar and ascorbic acid metabolism.

Although aerobic methane (CH4) release from plants leads to an intense scientific and public controversy in the recent years, the potential functions of endogenous CH4 production in plants are still largely unknown. Here, we reported that polyethylene glycol (PEG)-induced osmotic stress significantly increased CH4 production and soluble sugar contents in maize (Zea mays L.) root tissues. These enhancements were more pronounced in the drought stress-tolerant cultivar Zhengdan 958 (ZD958) than in the drought stress-sensitive cultivar Zhongjiangyu No.1 (ZJY1). Exogenously applied 0.65 mM CH4 not only increased endogenous CH4 production, but also decreased the contents of thiobarbituric acid reactive substances. PEG-induced water deficit symptoms, such as decreased biomass and relative water contents in both root and shoot tissues, were also alleviated. These beneficial responses paralleled the increases in the contents of soluble sugar and the reduced ascorbic acid (AsA), and the ratio of AsA/dehydroascorbate (DHA). Further comparison of transcript profiles of some key enzymes in sugar and AsA metabolism suggested that CH4 might participate in sugar signaling, which in turn increased AsA production and recycling. Together, these results suggested that CH4 might function as a gaseous molecule that enhances osmotic stress tolerance in maize by modulating sugar and AsA metabolism.

Molecular basis for the polyamine-ompF porin interactions: inhibitor and mutant studies.

By testing the sensitivity of Escherichia coli OmpF porin to various natural and synthetic polyamines of different lengths, charge and other molecular characteristics, we were able to identify the molecular properties required for compounds to act as inhibitors of OmpF in the nanomolar range. Inhibitors require at least two amine groups to be effective. For diamines, the optimum length of the hydrocarbon spacer was found to be of eight to ten methylene groups. Triamine molecules based on a 12-carbon motif were found to be more effective that spermidine, an eight-carbon trivalent derivative. But differences in inhibition efficiencies were also found for trivalent compounds depending on the relative position of the internal secondary amine group with respect to the terminal groups. Finally, quaternary ammonium derivatives had no effect, suggesting that the nature of the terminal amine is important for the interaction. From these observations, we deduce that inhibition efficiency in the nanomolar range requires a 12-carbon chain triamine with terminal primary amine groups and replacement of the eighth methylene by a secondary amine. The need for this type of molecular architecture suggests that inhibition is governed by interactions between specific amine groups and protein residues, and that this is not simply due to the accumulation of charges into the pore. Together with previous observations from site-directed mutagenesis studies and inspection of the crystal structure of OmpF, these results allowed us to propose three residues (D113, D121 and Y294) as putative sites of interaction between the channel and spermine. Alanine substitution at each of these three residues resulted in a loss of inhibition by spermine, while mutations of only D113 and D121 affected inhibition by spermidine. Based on these observations, we suggest a model for the molecular determinants involved in the porin-polyamine interaction.

The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies.

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver-carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into L-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.