Structurally Interesting Diarymethane Derivatives from Securidaca inappendiculata

Securines A—E, three dimeric diarymethane derivatives ( 1 — 3 ) and two enantiomeric diarymethane derivative monomers ( 4 and 5 ), were isolated and characterized from the medicinal plant Securidaca inappendiculata. Compounds 1 and 2 are a pair of enantiomeric diarymethane derivative dimers, and compound 3 is a mesomeric diarymethane derivative dimer. Their structures were determined by a combination of spectroscopic data, X‐ray crystallography, electronic circular dichroism (ECD) analysis, and computational ECD calculations. Dimeric compounds 1 — 3 showed moderate antiplasmodial activities with IC₅₀ values of 0.9, 1.4, and 1.5 μM, respectively.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Bioactive Properties and Phenolic Compound Profiles of Turnip-Rooted,Plain-Leafed and Curly-Leafed Parsley Cultivars

Petroselinum crispum Mill., Fuss., is a culinary vegetable used as an aromatic herb that garnishes and flavours a great variety of dishes. In the present study, the chemical profiles and bioactivities of leaf samples from 25 cultivars (three types: plain- and curly-leafed and turnip-rooted) from this species were assessed. Seven phenolic compounds were identified in all the varieties, including apigenin and kaempherol derivates. Apigenin-O-pentoside-O-hexoside was the major compound in all the tested parsley types (20, 22 and 13 mg/g of extract, respectively) and responsible for its excellent antioxidant activity, also investigated in this study. Antimicrobial activities were also explored, and the results revealed a good bioactivity against specific tested pathogens, such as bacteria and fungi. In conclusion, the leaves of all the types of P. crispum are a good source of natural bioactive compounds that confer health benefits, and thus, they should be part of a balanced and diversified diet.     

Saffron: Chemical Composition and Neuroprotective Activity

Crocus sativus L. belongs to the Iridaceae family and it is commonly known as saffron. The different cultures together with the geoclimatic characteristics of the territory determine a different chemical composition that characterizes the final product. This is why a complete knowledge of this product is fundamental, from which more than 150 chemical compounds have been extracted from, but only about one third of them have been identified. The chemical composition of saffron has been studied in relation to its efficacy in coping with neurodegenerative retinal diseases. Accordingly, experimental results provide evidence of a strict correlation between chemical composition and neuroprotective capacity. We found that saffron’s ability to cope with retinal neurodegeneration is related to: (1) the presence of specific crocins and (2) the contribution of other saffron components. We summarize previous evidence and provide original data showing that results obtained both “in vivo” and “in vitro” lead to the same conclusion.     

Sodium sulfate influence on the electrodeposition of MnO2 films for application in Supercapacitors

Journal of Solid State Electrochemistry - Manganese dioxide (MD) was synthesized by cyclic voltammetry using 0.5 mol L−1 MnSO4·6H2O as the precursor solution, with and...     

Determination of levofloxacin in pharmaceutical formulations and urine at reduced graphene oxide and carbon nanotube-modified electrodes

Journal of Solid State Electrochemistry - In this paper, we compare reduced graphene oxide (RGO) electrode with multi-walled carbon nanotubes (MWCNT) as modifiers for the sensitive detection of...     

Flow-through amperometric methods for detection of the bioactive compound quercetin: performance of glassy carbon and screen-printed carbon electrodes

Journal of Solid State Electrochemistry - Rapid methods using batch injection analysis (BIA) with amperometric detection were developed for the determination of quercetin extracted from the...     

Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid

Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent K_D of 50 nm  and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies.     

Dual Amperometric Immunosensor for Improving Cancer Metastasis Detection by the Simultaneous Determination of Extracellular and Soluble Circulating Fraction of Emerging Metastatic Biomarkers

This paper reports the development of a dual immunosensor using magnetic microcarriers (MBs) and amperometric transduction at dual screen‐printed carbon electrodes (SPdCEs) for the simultaneous determination of two biomarkers: interleukin‐13 receptor α2 (IL‐13Rα2) and E‐cadherin (E‐CDH), with both extracellular and soluble fraction; oncogenic and tumor suppressor markers, respectively, of great relevance in metastatic processes. The implemented methodology involved the formation of sandwich‐type immunocomplexes using specific capture antibodies immobilized onto carboxylic acid magnetic microbeads (HOOC‐MBs), and biotinylated detector antibodies labeled with streptavidin?horseradish peroxidase conjugates (Strep‐HRP). The amperometric detection was performed by addition of hydrogen peroxide in the presence of hydroquinone (HQ) as the redox mediator. The dual immunosensing platform provided linear calibration ranges suitable for the determination of both biomarkers in liquid and solid clinical specimens as well as excellent selectivity against other cancer biomarkers. This simple handling dual bioplatform was applied to the determination of the soluble and extracellular fraction of the target biomarkers in serum and paraffined‐embedded tissues from colorectal cancer (CRC) patients diagnosed at different tumor grade. The obtained results reveal great potential of this configuration to improve the reliability in diagnosing metastatic CRC.