Bioactive Properties of the Aqueous Extracts of Endophytic Fungi Associated with Scots Pine (Pinus sylvestris) Roots.

Despite the continuing interest in various plant and natural products, only a small portion of the biologically active compounds from nature has been discovered and exploited. In this study, antioxidant and antibacterial properties of aqueous fractions of three endophytic fungi isolated from the roots of 8-year-old Scots pines (Pinus sylvestris) growing on a drained peatland were investigated. The endophytic fungi species were Acephala applanata, Phialocephala fortinii, and Humicolopsis cephalosporioides/Coniochaeta mutabilis. The bioactivities were examined using hydrogen peroxide scavenging and oxygen radical absorbance capacity tests as well as sensitive Escherichia coli-based biosensors, which produce a luminescent signal in the presence of substances with oxidative or genotoxic properties. In addition, cell models for Parkinson's disease, age-related macular degeneration, and osteoarthritis were used to evaluate the potential for pharmaceutical applications. The aqueous extracts of fungi and 19 out of 42 fractions were found to be active in one or more of the tests used. However, no activity was found in the age-related macular degeneration and osteoarthritis cell model tests. Additionally, bioactivity data was connected with metabolites putatively annotated, and out of 330 metabolites, 177 were interesting in view of the bioactivities investigated. A majority of these were peptides and all three fungal species shared a highly similar metabolome. We propose that Scots pine endophytic fungi are a rich source of interesting metabolites, and synergistic effects may cause the bioactivities, as they were found to vary after the fractionation process.

Correction: Tienaho, J., et al. Metabolic Profiling of Water-Soluble Compounds from the Extracts of Dark Septate Endophytic Fungi (DSE) Isolated from Scots Pine (Pinus sylvestris L.) Seedlings Using UPLC-Orbitrap-MS. Molecules 2019, 24, 2330.

The authors wish to make the following corrections to this paper published in Molecules[...].

Metabolic Profiling of Water-Soluble Compounds from the Extracts of Dark Septate Endophytic Fungi (DSE) Isolated from Scots Pine (Pinus sylvestris L.) Seedlings Using UPLC-Orbitrap-MS.

Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi belonged to dark septate endophytes (DSE). The metabolic profiles of the hot water extracts of the fungi were investigated using Ultrahigh Performance Liquid Chromatography with Diode Array Detection and Electron Spray Ionization source Mass Spectrometry with Orbitrap analyzer (UPLC-DAD-ESI-MS-Orbitrap). Out of 318 metabolites, we were able to identify 220, of which a majority was amino acids and peptides. Additionally, opine amino acids, amino acid quinones, Amadori compounds, cholines, nucleobases, nucleosides, nucleotides, siderophores, sugars, sugar alcohols and disaccharides were found, as well as other previously reported metabolites from plants or endophytes. Some differences of the metabolic profiles, regarding the amount and identity of the found metabolites, were observed even though the fungi were isolated from the same host. Many of the discovered metabolites have been described possessing biological activities and properties, which may make a favorable contribution to the host plant nutrient availability or abiotic and biotic stress tolerance.

Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines.

Development of novel anticancer drugs is inevitable to improve treatment of cancers. In this study, novel derivatives of indoline and morpholine were synthesized and tested for their cytotoxic effects on osteosarcoma and Human Embryonic Kidney cells. To characterize cytotoxicity and the mechanism of cell death, we used cytotoxicity, migration, apoptosis markers and mitochondrial calcium assays. Among the compounds tested, the indoline derivatives, generally, produced a higher cytotoxic effect compared to the morpholine derivatives, in osteosarcoma cells. Specifically, new indoline derivative N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline exhibited effective cytotoxic activity, with an IC50 of ∼74 µM. The same molecule induced cell death by apoptosis and inhibited migration of the cells. Further, analysis of mitochondrial calcium levels revealed the existence of calcium dependent cell death mechanisms in different cell types. Therefore, N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline can be considered as a potential drug-lead compound towards the discovery of new anti-cancer agents.

Method with high-throughput screening potential for antioxidative substances using Escherichia coli biosensor katG'::lux.

A new method is described for the rapid real-time screening of antioxidative properties using a recombinant Escherichia coli DPD2511 biosensor. This microplate technique, without time-consuming pre-incubations and handling, has potential for a high-throughput search of bioactive compounds. Special emphasis was given to obtaining highly reliable and repeatable results.

Glycerol as an efficient medium for the petasis borono-mannich reaction.

The multicomponent Petasis borono-Mannich (PBM) reaction is a useful tool for the preparation of complex molecules in a single step from boronic acids, aldehydes/ketones, and amines. Here, we describe the use of glycerol in the PBM reaction of salicylaldehydes or 2-pyridinecarbaldehyde with several boronic acids and secondary amines. From these readily available starting materials, alkylaminophenols, 2-substituted pyridines, and 2H-chromenes were prepared in reasonable to good yields. Glycerol was compared with other solvents, and in some cases, it provided the reaction product in higher yield. Crude glycerol, as generated by the biodiesel industry, was evaluated and found to be a suitable solvent for the PBM reaction, successfully expanding the potential use of this industry by-product. Based on density functional theory (DFT) calculations and the obtained experimental results, the involvement of glycerol-derived boronic esters in the reaction mechanism is suggested to be competitive with the free boronic acid pathway. Similar Gibbs free energies for the aryl migration from the boronate species to the iminium were determined for both mechanisms.

Catalytic asymmetric total synthesis of tangutorine.

The first enantioselective total synthesis of tangutorine has been achieved, wherein a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand was the key step.

Mutagen structure and transcriptional response: induction of distinct transcriptional profiles in Salmonella TA100 by the drinking-water mutagen MX and its homologues.

The relationship between chemical structure and biological activity has been examined for various compounds and endpoints for decades. To explore this question relative to global gene expression, we performed microarray analysis of Salmonella TA100 after treatment under conditions of mutagenesis by the drinking-water mutagen MX and two of its structural homologues, BA-1, and BA-4. Approximately 50% of the genes expressed differentially following MX treatment were unique to MX; the corresponding percentages for BA-1 and BA-4 were 91 and 80, respectively. Among these mutagens, there was no overlap of altered Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways or RegulonDB regulons. Among the 25 Comprehensive Microbial Resource functions altered by these mutagens, only four were altered by more than one mutagen. Thus, the three structural homologues produced distinctly different transcriptional profiles, with none having a single altered KEGG pathway in common. We tested whether structural similarity between a xenobiotic and endogenous metabolites could explain transcriptional changes. For the 830 intracellular metabolites in Salmonella that we examined, BA-1 had a high degree of structural similarity to 2-isopropylmaleate, which is the substrate for isopropylmalate isomerase. The transcription of the gene for this enzyme was suppressed twofold in BA-1-treated cells. Finally, the distinct transcriptional responses of the three structural homologues were not predicted by a set of phenotypic anchors, including mutagenic potency, cytotoxicity, mutation spectra, and physicochemical properties. Ultimately, explanations for varying transcriptional responses induced by compounds with similar structures await an improved understanding of the interactions between small molecules and the cellular machinery.

Purine and sugar chemistry on solid phase--100 years after the Emil Fischer's Chemistry Nobel Prize 1902.

The Nobel Prize in Chemistry 1902 was given to Hermann Emil Fischer "in recognition of the extraordinary services he had rendered by his work on sugar and purine synthesis". This truly great chemist of all time named a group of bicyclic nitrogenous structures as purines, discovered the synthesis of glucose, fructose and mannose starting from glycerol, and further created the basis for glucoside-, amino acid-, and enzyme chemistry. To honour his discoveries, and to celebrate the 100 year since his Nobel Prize, we decided to write a short review article on the latest discoveries in the fields of purine/pyrimidine and sugar chemistry being performed on solid support. The review summarizes most of the material being published in the field since 1960, and ends by giving a picture of future directions for the field of drug discovery based on sugar and purine chemistry.