Sugar-Incorporated N-Heterocyclic-Carbene-Containing Gold(I) Complexes: Synthesis, Characterization, and Cytotoxic Evaluation

A series of neutral and cationic gold(I) complexes bearing a glucopyranoside-incorporated N-heterocyclic carbene (NHC) ligand are synthetized and structurally characterized. Different secondary ligands (chlorido, phosphane, or sugar–NHC) are employed to tune the properties of the complexes. The antiproliferative effects of the compounds are evaluated against PC-3 prostate cancer cells and a panel of human tumor cell lines. The activities of the phosphane complexes are comparable to that observed for cisplatin. The combined results provide further insights into the biological behavior of NHC–gold complexes

An Amphiphilic Pyridinoyl-hydrazone Probe for Colorimetric and Fluorescence pH Sensing

A new pH sensor based on a substituted aroylhydrazide with a flexible side chain and a terminal trimethyl ammonium group (PHA+) was designed and synthesized. The terminal quaternary ammonium guarantees excellent solubility in water. At the same time, the probe is very soluble in hydrophobic envirornments. The pyridinoyl-hydrazone moiety acts as the pH-sensitive fluorophore/chromophore probe. Extensive physicochemical characterization has been performed on the bromide salt PHABr. DFT calculations, based on single-crystal X-ray data, permitted to rationalize the optical behavior. Molecular dynamics simulations permitted to clarify the mode of interaction with lipid membrane. The ability of the probe to change color and fluorescence in response to different pH and media of different polarity has been investigated. PHABr shows a remarkable pH-dependent behavior in both absorption and fluorescence spectra with high sensitivity and strong on-off switch effect at neutral pH, perceptible even to the naked eye

A one-pot approach to novel pyridazine c-nucleosides

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2-and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside

7-hydroxytropolone is the main metabolite responsible for the fungal antagonism of Pseudomonas donghuensis strain SVBP6

Pseudomonas donghuensis strain SVBP6, an isolate from an agricultural plot in Argentina, displays a broad-spectrum and diffusible antifungal activity, which requires a functional gacS gene but could not be ascribed yet to known secondary metabolites typical of Pseudomonas biocontrol species. Here, we report that Tn5 mutagenesis allowed the identification of a gene cluster involved in both the fungal antagonism and the production of a soluble tropolonoid compound. The ethyl acetate extract from culture supernatant showed a dose-dependent inhibitory effect against the phytopathogenic fungus Macrophomina phaseolina. The main compound present in the organic extract was identified by spectroscopic and X-ray analyses as 7-hydroxytropolone (7HT). Its structure and tautomerism was confirmed by preparing the two key derivatives 2,3-dimethoxy- and 2,7-dimethoxy-tropone. 7HT, but not 2,3- or 2,7-dimethoxy-tropone, mimicked the fungal inhibitory activity of the ethyl acetate extract from culture supernatant. The activity of 7HT, as well as its production, was barely affected by the presence of up to 50 μM added iron (Fe+2). To summarize, P. donghuensis SVBP6 produces 7HT under the positive control of the Gac-Rsm cascade and is the main active metabolite responsible for the broad-spectrum inhibition of different phytopathogenic fungi.Fil: Muzio, Federico Matías. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Centro de Bioquimica y Microbiologia de Suelos. Laboratorio de Fisiologia, Genetica de Bacterias Para Plantas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Agaras, Betina Cecilia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Centro de Bioquimica y Microbiologia de Suelos. Laboratorio de Fisiologia, Genetica de Bacterias Para Plantas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Masi, Marco. Università degli Studi di Napoli Federico II; ItaliaFil: Tuzi, Angela. Università degli Studi di Napoli Federico II; ItaliaFil: Evidente, Antonio. Università degli Studi di Napoli Federico II; ItaliaFil: Valverde, Claudio Fabián. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Centro de Bioquimica y Microbiologia de Suelos. Laboratorio de Fisiologia, Genetica de Bacterias Para Plantas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Higginsianins A and B, Two Diterpenoid α-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity

Two new diterpenoid α-pyrones, named higginsianins A (1) and B (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)dodecahydronaphtho[2,1-b]furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)decahydronaphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (1) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (2), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. 1 and 2 were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of 1 and 2 for antiproliferative activity against a panel of six cancer cell lines revealed that the IC50 values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 μM). Finally, three hemisynthetic derivatives of 1 were prepared and evaluated for antiproliferative activity. Two of these possessed IC50 values and differential sensitivity profiles similar to those of 1

In Vitro and In Vivo Toxicity Evaluation of Natural Products with Potential Applications as Biopesticides

The use of natural products in agriculture as pesticides has been strongly advocated. However, it is necessary to assess their toxicity to ensure their safe use. In the present study, mammalian cell lines and fish models of the zebrafish (Danio rerio) and medaka (Oryzias latipes) have been used to investigate the toxic effects of ten natural products which have potential applications as biopesticides. The fungal metabolites cavoxin, epi-epoformin, papyracillic acid, seiridin and sphaeropsidone, together with the plant compounds inuloxins A and C and ungeremine, showed no toxic effects in mammalian cells and zebrafish embryos. Conversely, cyclopaldic and α-costic acids, produced by Seiridium cupressi and Dittrichia viscosa, respectively, caused significant mortality in zebrafish and medaka embryos as a result of yolk coagulation. However, both compounds showed little effect in zebrafish or mammalian cell lines in culture, thus highlighting the importance of the fish embryotoxicity test in the assessment of environmental impact. Given the embryotoxicity of α-costic acid and cyclopaldic acid, their use as biopesticides is not recommended. Further ecotoxicological studies are needed to evaluate the potential applications of the other compounds

Interpretare e costruire mondi: pratiche inclusive a varie latitudini

Il contributo delle discipline umanistiche si rivela oggi più che mai essenziale per poter leggere e interpretare la complessità del mondo contemporaneo. Le molteplici crisi che hanno segnato la storia moderna e contemporanea hanno fatto (ri)emergere pericolose narrative di esclusione che intellettuali ed artisti si sono sentiti chiamati a decostruire. A fronte di diverse forme di marginalizzazione, pratiche di censura e di disuguaglianza sociale, la produzione culturale e artistica ha tentato di (ri)costruire nuove forme di solidarietà e di offrire nuove prospettive di miglioramento comune. Il numero 2/2022 della rivista DIVE-IN – An International Journal on Diversity and Inclusion contiene otto contributi, uniti dal fil rouge dell’inclusione, che offrono una interessante panoramica dei tentativi di (ri)costruzione che si articolano in diversi campi espressivi a varie latitudini geografiche e tematico-disciplinari