Antimicrobial activity and phenolic content of natural site and micropropagated Limonium avei (De Not.) Brullo & Erben plant extracts

This study reported the antimicrobial activity and phenolic content of natural site and micropropagated Limonium avei (De Not.) Brullo & Erben inflorescences. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ethanolic extracts were determined according to the Clinical Laboratory Standards Institute guidelines. Individual phenolic acids and flavonoids were detected by a high performance liquid chromatography (HPLC-DAD) method. The samples showed a comparable antimicrobial activity, although the natural site extract possessed the lower MIC values. The best activity was detected against Gram-positive bacteria, such as Staphylococcus aureus including methicillin resistant strains (MIC and MBC values ranging from 7.81 to 62.50?μg?mL(-1) and from 500 to 2000?μg?mL(-1) respectively). In contrast, a low activity was found on Gram-negative bacteria and Candida albicans. The HPLC-DAD analysis revealed ten phenolic acids and four flavonoids with a major amount of m-coumaric acid, naringin and quercetin in the natural site extract.     

Characterization of rhinovirus subviral A particles via capillary electrophoresis, electron microscopy and gas-phase electrophoretic mobility molecular analysis: Part I

During infection, enteroviruses, such as human rhinoviruses (HRVs), convert from the native, infective form with a sedimentation coefficient of 150S to empty subviral particles sedimenting at 80S (B particles). B particles lack viral capsid protein 4 (VP4) and the single-stranded RNA genome. On the way to this end stage, a metastable intermediate particle is observed in the cell early after infection. This subviral A particle still contains the RNA but lacks VP4 and sediments at 135S. Native (150S) HRV serotype 2 (HRV2) as well as its empty (80S) capsid have been well characterized by capillary electrophoresis. In the present paper, we demonstrate separation of at least two forms of subviral A particles on the midway between native virions and empty 80S capsids by CE. For one of these intermediates, we established a reproducible way for its preparation and characterized this particle in terms of its electrophoretic mobility and its appearance in transmission electron microscopy (TEM). Furthermore, the conversion of this intermediate to 80S particles was investigated. Gas-phase electrophoretic mobility molecular analysis (GEMMA) yielded additional insights into sample composition. More data on particle characterization including its protein composition and RNA content (for unambiguous identification of the detected intermediate as subviral A particle) will be presented in the second part of the publication.     

Enantioselective total synthesis of (-)-acetylaranotin, a dihydrooxepine epidithiodiketopiperazine

The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (-)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (-)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family.     

Reversible gas-phase redox processes catalyzed by Co-exchanged MFU-4l(arge)

Postsynthetic metal ion exchange in a benzotriazolate-based MFU-4l(arge) framework leads to a Co(II)-containing framework with open metal sites showing reversible gas-phase oxidation properties.     

Electronic excitations and lattice dynamics of coordinatively "unsaturated" complex transition metal compounds

Single crystal polarized Raman and infrared spectra of the series Na(5)[MO(2)][X] with M = Co(I), Ni(I), and Cu(I) and X = S(2-) and CO(3)(2-), are reported. All phonon modes are assigned to the lattice eigenmodes based on the group theory analysis and first principles lattice dynamics calculations. The energies of the fundamental symmetric and asymmetric vibrations of the [MO(2)](3-) complex are discussed on the basis of their electronic structure and variation in M-O interatomic distances. Electronic Raman scattering and luminescence are observed for the magnetic members of the series (Co(I), d(8), and Ni(I), d(9)). Ligand field theory is employed to account for the electronic effects which originate from states split by spin-orbit coupling.     

Identification of Ros Produced by Photodynamic Activity of Chlorophyll/Cyclodextrin Inclusion Complexes

Photodynamic therapy (PDT) is a way of treating malignant tumors and hyperproliferative diseases. It is based on the use of photosensitizer, herein the chlorophyll a (chl a), and a light of an appropriate wavelength. The interaction of the photosensitizer (PS) with the light produces reactive oxygen species (ROS), powerful oxidizing agents, which cause critical damage to the tissue. To solubilize chl a in aqueous solution and to obtain it as monomer, we have used cyclodextrins, carriers which are able to interact with the pigment and form the inclusion complex. The aim of this study is to examine which types of ROS are formed by Chl a/cyclodextrin complexes in phosphate buffered solution and cell culture medium, using specific molecules, called primary acceptors, which react selectively with the reactive species. In fact the changes of the absorption and the emission spectra of these molecules after the illumination of the PS provide information on the specific ROS formation. The ¹O₂ formation has been tested using chemical methods based on the use of Uric Acid (UA), 9,10‐diphenilanthracene (DPA) and Singlet oxygen sensor green (SOSG) and by direct detection of Singlet Oxygen (¹O₂) luminescence decay at 1270 nm. Moreover, 2,7‐dichlorofluorescin and ferricytochrome c (Cyt Fe³⁺) have been used to detect the formation of hydrogen peroxide and superoxide radical anion, which reduces Fe³⁺ of the ferricytochrome to Fe²⁺, respectively.     

Characterization of <Emphasis Type="Italic">Pf</Emphasis>TrxR inhibitors using antimalarial assays and <Emphasis Type="Italic">in silico</Emphasis>techniques

Background

The compounds 1,4-napthoquinone (1,4-NQ), bis-(2,4-dinitrophenyl)sulfide (2,4-DNPS), 4-nitrobenzothiadiazole (4-NBT), 3-dimethylaminopropiophenone (3-DAP) and menadione (MD) were tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay and also for analysis of non-covalent interactions with P. falciparum thioredoxin reductase (PfTrxR) through in silico docking studies.

Results

The inhibitors of PfTrxR namely, 1,4-NQ, 4-NBT and MD displayed significant antimalarial activity with IC₅₀ values of?<?20 μM and toxicity against 3T3 cell line. 2,4-DNPS was only moderately active. In silico docking analysis of these compounds with PfTrxR revealed that 2,4-DNPS, 4-NBT and MD interact non-covalently with the intersubunit region of the enzyme.

Conclusions

In this study, tools for the identification of PfTrxR inhibitors using phenotyphic screening and docking studies have been validated for their potential use for antimalarial drug discovery project.

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A Convenient and Rapid Preparation of Novel Quinoxaline Derivatives

A simple and rapid method for the preparation of a series of novel quinoxaline derivatives in the presence of Ag⁺ is reported.     

The Preparation Of 2-[4,5-Dihydro-3-Aryl-5-Isoxazolyl]-Phenols From C(α),O-Dilithiooximes and Lithiated Hydroxyaryl Aldehydes

C(a), O-Oximes were dilithiated in excess lithium diisopropylamide, and the resulting intermediates were condensed with lithiated hydroxyphenyl aldehydes and related materials and cyclized with acid to afford 2-[4,5-dihydro-3-aryl-5-isoxazolyl]phenols, substituted 4,5-dihydroisoxazoles (2-isoxazolines).     

Cyclometalated AuIII Complexes for Cysteine Arylation in Zinc Finger Protein Domains: towards Controlled Reductive Elimination

With the aim of exploiting the use of organometallic species for the efficient modification of proteins through C-atom transfer, the gold-mediated cysteine arylation through a reductive elimination process occurring from the reaction of cyclometalated Au^III C^N complexes with a zinc finger peptide (Cys₂His₂ type) is here reported. Among the four selected Au^III cyclometalated compounds, the [Au(C^CON)Cl₂] complex featuring the 2-benzoylpyridine (C^CON) scaffold was identified as the most prone to reductive elimination and Cys arylation in buffered aqueous solution (pH 7.4) at 37 °C by high-resolution LC electrospray ionization mass spectrometry. DFT and quantum mechanics/molecular mechanics (QM/MM) studies permitted to propose a mechanism for the title reaction that is in line with the experimental results. Overall, the results provide new insights into the reactivity of cytotoxic organogold compounds with biologically important zinc finger domains and identify initial structure–activity relationships to enable Au^III-catalyzed reductive elimination in aqueous media.