bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyhedral [M2B5] Metallaborane Clusters and Derivatives: An Overview of Their Structural Features and Chemical Bonding
Authors: Prakash Rini , Halet Jean-François , Ghosh Sundargopal
Published: July 2020

A large number of metallaborane clusters and their derivatives with various structural arrangements are known. Among them, M2B5 clusters and derivatives constitute a significant class. Transition metals present in these species span from group 4 to group 7. Their structure can vary from oblatonido, oblatoarachno, to arachno type open structures. Many of these clusters appear to be hypoelectronic and are often considered as ‘rule breakers’ with respect to the classical Wade–Mingos electron counting rules. This is due to their unique highly oblate (flattened) deltahedral structures featuring a cross-cluster M−M interaction. Many theoretical calculations were performed to elucidate their electronic structure and chemical bonding properties. In this review, the synthesis, structure, and electronic aspects of the transition metal M2B5 clusters known in the literature are discussed. The chosen examples illustrate how, in synergy with experiments, computational results can provide additional valuable information to better understand the electronic properties and electronic requirements which govern their architecture and thermodynamic stability.
Design, Synthesis and Anti-Tumor Activity of Novel Benzimidazole-Chalcone Hybrids as Non-Intercalative Topoisomerase II Catalytic Inhibitors
Authors: Zhou Wei , Zhang Wenjin , Peng Yi , Jiang Zhi-Hong , Zhang Lanyue , Du Zhiyun
Published: July 2020

Chemical diversification of type II topoisomerase (Topo II) inhibitors remains indispensable to extend their anti-tumor therapeutic values which are limited by their side effects. Herein, we designed and synthesized a novel series of benzimidazole-chalcone hybrids (BCHs). These BCHs showed good inhibitory effect in the Topo II mediated DNA relaxation assay and anti-proliferative effect in 4 tumor cell lines. 4d and 4n were the most potent, with IC50 values less than 5 μM, superior to etoposide. Mechanistic studies indicated that the BCHs functioned as non-intercalative Topo II catalytic inhibitors. Moreover, 4d and 4n demonstrated versatile properties against tumors, including inhibition on the colony formation and cell migration, and promotion of apoptosis of A549 cells. The structure-activity relationship and molecular docking analysis suggested possible contribution of the chalcone motif to the Topo II inhibitory and anti-proliferative potency. These results indicated that 4d and 4n could be promising lead compounds for further anti-tumor drug research.
Preferential Orientation of Photochromic Gadolinium Oxyhydride Films
Authors: Baba Elbruz Murat , Montero Jose , Moldarev Dmitrii , Moro Marcos Vinicius , Wolff Max , Primetzhofer Daniel , Sartori Sabrina , Zayim Esra , Karazhanov Smagul
Published: July 2020

We report preferential orientation control in photochromic gadolinium oxyhydride (GdHO) thin films deposited by a two-step process. Gadolinium hydride (GdH2-x) films were grown by reactive magnetron sputtering, followed by oxidation in air. The preferential orientation, grain size, anion concentrations and photochromic response of the films were strongly dependent on the deposition pressure. The GdHO films showed a preferential orientation along the [100] direction and exhibited photochromism when synthesized at deposition pressures of up to 5.8 Pa. The photochromic contrast was larger than 20% when the films were deposited below 2.8 Pa with a 0.22 H2/Ar flow ratio. We argue that the relation of preferential orientation and the post deposition oxidation since oxygen concentration is known to be a key parameter for photochromism in rare-earth oxyhydride thin films. The experimental observations described above were explained by the decrease of the grain size as a result of the increase of the deposition pressure of the sputtering gas, followed by a higher oxygen incorporation.
Versatile Polypeptide-Functionalized Plasmonic Paper as Synergistic Biocompatible and Antimicrobial Nanoplatform
Authors: Tie Leopold , Răileanu Mina , Bacalum Mihaela , Codita Irina , Negrea Ștefania Mădălina , Caracoti Costin Ștefan , Drăgulescu Elena-Carmina , Campu Andreea , Astilean Simion , Focsan Monica
Published: July 2020

Nowadays, thanks to nanotechnological progress, which itself guides us more and more closely toward not only the efficient design of innovative nanomaterials or nanostructures, but to the improvement of their functionality, we benefit from an important asset in the battle against pathogenic illnesses. Herein, we report a versatile biocompatible plasmonic nanoplatform based on a Whatman paper incorporating positively-charged gold nanospherical particles via the immersion approach. The morphological characterization of the as-engineered-plasmonic paper was examined by SEM (scanning electron microscopy) and HRTEM (high-resolution transmission electron microscopy) investigations, while its surface chemical modification with a synthetic polypeptide, specifically RRWHRWWRR-NH2 (P2), was proved by monitoring the plasmonic response of loaded gold nanospheres and the emission signal of P2 via fluorescence spectroscopy. The as-functionalized plasmonic paper is non-cytotoxic towards BJ fibroblast human cells at bactericidal concentrations. Finally, the antimicrobial activity of the P2-functionalized plasmonic paper on both planktonic bacteria and biofilms was tested against two reference strains: Gram-positive Bacteria, i.e., Staphylococcus aureus and the Gram-negative Bacteria, i.e., Escherichia coli, determining microbial inhibition of up to 100% for planktonic bacteria. In line with the above presented nanoplatform’s proper design, followed by their functionalization with active antimicrobial peptides, new roads can be open for determining antibiotic-free treatments against different relevant pathogens.
New Copper(I) Complex with a Coumarin as Ligand with Antibacterial Activity against Flavobacterium psychrophilum
Authors: Aldabaldetrecu Maialen , Parra Mick , Soto Sarita , Arce Pablo , Tello Mario , Guerrero Juan , Modak Brenda
Published: July 2020

A new copper (I) complex, [Cu(NN1)2](ClO4), was synthesized, where NN1 was a imine ligand 6-((quinolin-2-ylmethylene)amino)-2H-chromen-2-one obtained by a derivatization of natural compound coumarin. The structural characterization in solution was done by NMR techniques, UV-Vis and cyclic voltammetry. The potential antibacterial effect of [Cu(NN1)2](ClO4), was assessed for F. psychrophilum isolated 10094. F. psychrophilum is a Gram-negative bacterium which causes diseases such as bacterial cold-water disease and rainbow trout fry syndrome, causing large economic losses in the freshwater salmonid aquaculture industry. This complex show to have antibacterial activity against F. psychrophilum 10094 at non-cytotoxic concentration in cell line derived from trout (F. psychrophilum 10094 IC50 16.0 ± 0.9; RT-GUT IC50 53.0 ± 3.1 µg/mL).
Effect of Naringenin and Its Derivatives on the Probing Behavior of Myzus persicae (Sulz.)
Authors: Stec Katarzyna , Kozłowska Joanna , Wróblewska-Kurdyk Anna , Kordan Bożena , Anioł Mirosław , Gabryś Beata
Published: July 2020

Substances that alter insect behavior have attracted a lot of attention as potential crop protection agents. Naringenin (5,7,4′-trihydroxyflavanone) is a naturally occurring bioactive flavanone. We evaluated the influence of naringenin on aphid activities during individual phases of probing and feeding and the effect of structural modifications of naringenin on its activity towards aphids. We monitored the probing behavior of Myzus persicae (Sulz.) (Hemiptera: Aphididae) using the Electrical Penetration Graph (EPG) technique. The chemical modifications were the substitution of hydrogen atoms with methyl, ethyl or pentyl groups and the replacement of the carbonyl group in naringenin and its derivatives with an oxime moiety. Depending on the substituents, the activity of naringenin-derived compounds varied in potency and mode of action. Naringenin was an attractant of moderate activity, which enhanced sap ingestion. The naringenin derivative with two methyl groups—7,4′-di-O-methylnaringenin—was a deterrent, which hindered aphid probing in non-phloem tissues. Naringenin oxime derivatives with methyl substituents—7,4′-di-O-methylnaringenin oxime, 7-O-methylnaringenin oxime, and 5,7,4′-tri-O-methylnaringenin oxime—and the derivative with a pentyl substituent—7-O-pentylnaringenin oxime—were strong attractants which stimulated aphid probing in non-phloem tissues and the ingestion of phloem sap.
Antioxidant, Antimicrobial, and Other Biological Properties of Pompia Juice
Authors: Barberis Antonio , Deiana Monica , Spissu Ylenia , Azara Emanuela , Fadda Angela , Serra Pier Andrea , D’hallewin Guy , Pisano Marina , Serreli Gabriele , Orrù Germano , Scano Alessandra , Steri Daniela , Sanjust Enrico
Published: July 2020

Pompia is a Citrus species belonging to Sardinian endemic biodiversity. Health benefits were attributed to its flavedo rind extracts and essential oils while the juice qualities have never been investigated. In this paper, the antioxidant, antimicrobial, and other biological properties of Pompia juice were studied. A combined LCMS/electrochemical/biological approach was used to clarify a still debated phylogeny of this species and to explain the role of its juice phenolic compounds. A closer phylogenetic relationship with lemon and citron, rather than oranges was suggested. Sensors-based electrochemical measures, together with LCMS qualitative and quantitative analyses, revealed a high contribution of ascorbic acid and phenolics with low redox potential, isorhamnetin 3-O-rutinoside, diosmin, and diosmetin 6,8-diglucoside, to antioxidant capacity. The biological assays demonstrated a marked effect of low concentration of Pompia juice against reactive oxygen species (ROS) starting from 50 µg mL−1, and a moderate capacity to reduce ROS damages on cell membrane. Treatments with Pompia juice also resulted in a significant reduction (20%) of the metabolic activity of SW48 colon cancer cells. Lastly, MIC, MBC, and MBIC antimicrobial assays demonstrated that Pompia and lemon juices have inhibitory and antibiofilm effects against the pathogenic bacteria Pseudomonas aeruginosa, Streptococcus aureus, and Enterococcus faecalis.
Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities
Authors: Shaik Afzal B. , Bhandare Richie R. , Nissankararao Srinath , Edis Zehra , Tangirala N. Ravikiran , Shahanaaz Shaik , Rahman M. Mukhlesur
Published: July 2020

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC50 value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities.
Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer’s Disease Therapy
Authors: Zribi Lazhar , Pachòn-Angona Irene , Bautista-Aguilera Òscar M. , Diez-Iriepa Daniel , Marco-Contelles José , Ismaili Lhassane , Iriepa Isabel , Chabchoub Fakher
Published: July 2020

Alzheimer’s disease (AD) is multifactorial disease characterized by the accumulation of abnormal extracellular deposits of amyloid-beta (Aβ) peptide, and intracellular neurofibrillary tangles (NFTs), along with dramatic neuronal death and decreased levels of choline acetyltransferase. Given the limited therapeutic success of available drugs, it is urgent to explore all the opportunities available to combat this illness. Among them, the discovery of new heterocyclic scaffolds binding different receptors involved in AD should offer structural diversity and new therapeutic solutions. In this context, this work describes new triazolopyridopyrimidine easily prepared in good yields showing anticholinesterase inhibition and strong antioxidant power, particularly the most balanced: 6-amino-5-(4-methoxyphenyl)-2-phenyl-[1,2,4]triazolo[1′,5′:1,6] pyrido[2,3-d]pyrimidine-4-carbonitrile(3c) with IC50 equal to 1.32 μM against AChE and oxygen radical absorbance capacity (ORAC) value equal to 4.01 Trolox equivalents (TE); thus representing a new and very promising hit-triazolopyridopyrimidine for AD therapy.
Formulation of a Phenol-Rich Extract from Unripe Olives (Olea europaea L.) in Microemulsion to Improve Its Solubility and Intestinal Permeability
Authors: Cecchi Lorenzo , Piazzini Vieri , D’Ambrosio Mario , Luceri Cristina , Rocco Federica , Innocenti Marzia , Vanti Giulia , Mulinacci Nadia , Bergonzi Maria Camilla
Published: July 2020

The beneficial properties of phenolic compounds from Olea europaea L. are well-known. An olive extract (OE) was prepared from unripe olives (Moraiolo cultivar). The study aimed to formulate OE into a microemulsion (ME) in oral dosage form. OE was extracted from olives with EtOH:H2O (80:20) and characterized by HPLC-DAD. ME composition was stated by a solubility and pseudo-ternary diagram. The ME was chemically and physically characterized, and its stability at 4 °C was analyzed for three months. The ability of the formulation to ameliorate the solubility and the intestinal permeability of OE was evaluated by a Parallel Artificial Membrane Permeability Assay (PAMPA) assay and Caco-2 cells. The total phenolic content of the extract was 39% w/w. The main constituent was oleuropein (31.0%), together with ligstroside (3.1%) and verbascoside (2.4%). The ME was prepared using Capryol 90 as the oily phase, and Cremophor EL and Transcutol (2:1) as surfactant and co-surfactant, respectively. ME droplet size was 14.03 ± 1.36 nm, PdI 0.20 ± 0.08, ζ-potential −1.16 ± 0.48. Stability of ME was confirmed for at least three months. The formulation was loaded with 35 mg/mL of OE, increasing the solubility of the extract by about four times. The enhanced permeability of OE was evaluated by PAMPA, as demonstrated by the Pe value (1.44 ± 0.83 × 10−6 cm/s for OE hydroalcoholic solution, 3.74 ± 0.34 × 10−6 cm/s for OE-ME). Caco-2 cell transport studies confirmed the same results: Papp was 16.14 ± 0.05 × 10−6 cm/s for OE solution and 26.99 ± 0.45 × 10−6 cm/s for OE-ME. ME proved to be a suitable formulation for oral delivery.
Herbivory and Attenuated UV Radiation Affect Volatile Emissions of the Invasive Weed Calluna vulgaris
Authors: Effah Evans , Barrett D. Paul , Peterson Paul G. , Wargent Jason J. , Potter Murray A. , Holopainen Jarmo K. , Clavijo McCormick Andrea
Published: July 2020

Calluna vulgaris (heather) is an aggressive invasive weed on the Central Plateau, North Is., New Zealand (NZ), where it encounters different environmental factors compared to its native range in Europe, such as high ultraviolet radiation (UV) and a lack of specialist herbivores. The specialist herbivore Lochmaea suturalis (heather beetle) was introduced from the United Kingdom (UK) in 1996 as a biocontrol agent to manage this invasive weed. Like other plant invaders, a novel environment may be challenging for heather as it adjusts to its new conditions. This process of “adjustment” involves morphological and physiological changes often linked to phenotypic plasticity. The biochemical responses of exotic plants to environmental variables in their invaded range is poorly understood. The production and release of volatile organic compounds (VOCs) is essential to plant communication and highly susceptible to environmental change. This study therefore aimed to explore the VOC emissions of heather in response to different levels of UV exposure, and to feeding damage by L. suturalis. Using tunnel houses clad with UV-selective filters, we measured VOCs produced by heather under NZ ambient, 20% attenuated, and 95% attenuated solar UV treatments. We also compared VOC emissions in the field at adjacent sites where L. suturalis was present or absent. Volatiles produced by the same target heather plants were measured at four different times in the spring and summer of 2018–2019, reflecting variations in beetle’s abundance, feeding stage and plant phenology. Heather plants under 95% attenuated UV produced significantly higher amounts of (E)-β-farnesene, decanal, benzaldehyde, and benzeneacetaldehyde compared to 25% attenuated and ambient UV radiation. We also found significant differences in volatiles produced by heather plants in beetle-present versus beetle-absent sites on most sampling occasions. We also recorded a lower number of generalist herbivores on heather at sites where L. suturalis was present. Interactions between invasive plants, a novel environment, and the native communities they invade, are discussed.
Antianhedonic and Antidepressant Effects of Affron®, a Standardized Saffron (Crocus Sativus L.) Extract
Authors: Orio Laura , Alen Francisco , Ballesta Antonio , Martin Raquel , Gomez de Heras Raquel
Published: July 2020

Anxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron®, a standardized saffron extract containing ≥3.5% of total bioactive compounds safranal and crocin isomers. Affron® was administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affron® displayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.
In Vitro Anticancer and Radiosensitizing Activities of Phlorethols from the Brown Alga Costaria costata
Authors: Malyarenko Olesya S. , Imbs Tatiana I. , Ermakova Svetlana P.
Published: July 2020

The anticancer and radiosensitizing effects of high-molecular-weight phlorethols CcPh (Mw = 2520 Da) isolated from the brown algae of Costaria costata on human colorectal carcinoma HCT 116 and HT-29 cells were investigated. Phlorethols CcPh possessed cytotoxic activity against HT-29 (IC50 = 92 μg/mL) and HCT 116 (IC50 = 94 μg/mL) cells. CcPh at non-toxic concentrations inhibited the colony formation in colon cancer cells and significantly enhanced their sensitivity to low non-toxic X-ray irradiation. The combinatory effect of radiation and CcPh was synergistic (Combination index < 0.7). Algal phlorethols might be prospective candidates as radiosensitizers to improve the scheme of radiotherapy.
Study of the Reactivity of Lignin Model Compounds to Fluorobenzylation Using 13C and 19F NMR: Application to Lignin Phenolic Hydroxyl Group Quantification by 19F NMR
Authors: Esakkimuthu Esakkiammal Sudha , Marlin Nathalie , Brochier-Salon Marie-Christine , Mortha Gérard
Published: July 2020

Lignin is an aromatic biopolymer derived from lignocellulosic biomass. Providing a comprehensive structural analysis of lignin is the primary motivation for the quantification of various functional groups, with a view to valorizing lignin in a wide range of applications. This study investigated the lignin fluorobenzylation reaction and performed a subsequent 19F-NMR analysis to quantify hydroxyl groups, based on a work developed two decades ago by Barrelle et al. The objectives were to check the assignments proposed in this previous study and to examine the reactivity of various types of lignin hydroxyls with the derivatization agent. Selected lignin model compounds containing phenolic and aliphatic hydroxyls were subjected to the fluorobenzylation reaction, and the obtained reaction medium was analyzed by 13C and 19F NMR spectroscopy. The model compound results showed that phenolic hydroxyls were totally derivatized, whereas aliphatic hydroxyls underwent minimal conversion. They also confirmed that 19F NMR chemical shifts from −115 ppm to −117.3 ppm corresponded to phenolic groups. Then, a 19F NMR analysis was successfully applied to Organosolv commercial lignin after fluorobenzylation in order to quantify its phenolic group content; the values were found to be in the range of the reported values using other analytical techniques after lignin acetylation.
Testing the Applicability of MALDI-TOF MS as an Alternative Stock Identification Method in a Cryptic Species Complex
Authors: Maasz Gabor , Zrínyi Zita , Fodor Istvan , Boross Nóra , Vitál Zoltán , Kánainé Sipos Dóra Ildikó , Kovács Balázs , Melegh Szilvia , Takács Péter
Published: July 2020

Knowledge of intraspecific variability of a certain species is essential for their long-term survival and for the development of conservation plans. Nowadays, molecular/genetic methods are the most frequently used for this purpose. Although, the Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) technique has become a promising alternative tool to specify intraspecific variability, there is a lack of information about the limitations of this method, and some methodological issues need to be resolved. Towards this goal, we tested the sensitivity of this method on an intraspecific level, using genetically identified individuals of a cryptic fish species complex collected from five distinct populations. Additionally, some methodologic issues, such as the effect of (1) delayed sample preparation, (2) clove oil anaesthetization, and (3) different tissue types (muscle, and brain) were investigated using the MS analysis results. Our results show that the delayed sample preparation has a fundamental effect on the result of MS analysis, while at the same time the clove oil did not affect the results considerably. Both the brain and muscle samples were usable for cryptic species identification, but in our opinion this method has limited applicability for population-level segregation. The application of MALDI-TOF MS to the exploitable toolkit of phylogenetic and taxonomic researches could be used to broaden conclusions.
Application of Deep Eutectic Solvents and Ionic Liquids in the Extraction of Catechins from Tea
Authors: Bajkacz Sylwia , Adamek Jakub , Sobska Anna
Published: July 2020

This work aimed to comprehensively evaluate the potential and effectiveness of deep eutectic solvents (DESs) in the extraction of seven catechins from various tea samples. Different combinations of DES were used, consisting of Girard’s reagent T (GrT) in various mixing ratios with organic acids and choline chloride. The yields of the DES extractions were compared with those from ionic liquids and conventional solvent. DES contained malic acid, as the hydrogen bond donors showed a good solubility of catechins with different polarities. In the second part of the study, a solid-phase extraction (SPE) method was applied to the extraction of catechins from tea infusions. The method was applied to the determination of selected catechins in tea leaves and tea infusions. Furthermore, we demonstrated that the proposed procedure works well in the simultaneous monitoring of these polyphenols, which makes it a useful tool in the quality control of tea.
Scalable Green Approach Toward Fragrant Acetates
Authors: Puchl’ová Eva , Szolcsányi Peter
Published: July 2020

The advantageous properties of ethylene glycol diacetate (EGDA) qualify it as a useful substitute for glycerol triacetate (GTA) for various green applications. We scrutinised the lipase-mediated acetylation of structurally diverse alcohols in neat EGDA furnishing the range of naturally occurring fragrant acetates. We found that such enzymatic system exhibits high reactivity and selectivity towards activated (homo) allylic and non-activated primary/secondary alcohols. This feature was utilised in the scalable multigram synthesis of fragrant (Z)-hex-3-en-1-yl acetate in 70% yield. In addition, the Lipozyme 435/EGDA system was also found to be applicable for the chemo-selective acetylation of (hydroxyalkyl) phenols as well as for the kinetic resolution of chiral secondary alcohols. Lastly, its discrimination power was demonstrated in competitive experiments of equimolar mixtures of two isomeric alcohols. This enabled the practical synthesis of 1-pentyl acetate isolated as a single product in 68% yield from the equimolar mixture of 1-pentanol and 3-pentanol.
Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications
Authors: El-Sharkawy Ahmed , Malki Ahmed
Published: July 2020

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.
Chemometric and Transcriptomic Profiling, Microtubule Disruption and Cell Death Induction by Secalonic Acid in Tumor Cells
Authors: Özenver Nadire , Dawood Mona , Fleischer Edmond , Klinger Anette , Efferth Thomas
Published: July 2020

Nature is an indispensable source of new drugs, providing unique bioactive lead structures for drug discovery. In the present study, secalonic acid F (SAF), a naturally occurring ergochrome pigment, was studied for its cytotoxicity against various leukemia and multiple myeloma cells by the resazurin assay. SAF exhibited cytotoxic activity on both leukemia and multiple myeloma cells. Generally, multiple myeloma cells were more sensitive to SAF than leukemia cells. NCI-H929 cells were the most affected cells among the tested panel of multiple myeloma cell lines and were taken for further studies to assess the mode of action of SAF on those cells. Cell cycle analysis revealed that SAF induced S and G2/M arrest in NCI-H929 cells. SAF-associated apoptosis and necrosis resulted in cytotoxicity. SAF further inclined the disassembly of the tubulin network, which may also account for its cytotoxicity. COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of the NCI tumor cell line panel identified genes involved in numerous cellular processes (e.g., cell differentiation, cell migration, and other numerous signaling pathways) notably correlated with log10IC50 values for secalonic acid. In conclusion, the present study supports the therapeutic potential of SAF to treat multiple myeloma.
Comparative Assessment of Protein Kinase Inhibitors in Public Databases and in PKIDB
Authors: Bournez Colin , Carles Fabrice , Peyrat Gautier , Aci-Sèche Samia , Bourg Stéphane , Meyer Christophe , Bonnet Pascal
Published: July 2020

Since the first approval of a protein kinase inhibitor (PKI) by the Food and Drug Administration (FDA) in 2001, 55 new PKIs have reached the market, and many inhibitors are currently being evaluated in clinical trials. This is a clear indication that protein kinases still represent major drug targets for the pharmaceutical industry. In a previous work, we have introduced PKIDB, a publicly available database, gathering PKIs that have already been approved (Phase 4), as well as those currently in clinical trials (Phases 0 to 3). This database is updated frequently, and an analysis of the new data is presented here. In addition, we compared the set of PKIs present in PKIDB with the PKIs in early preclinical studies found in ChEMBL, the largest publicly available chemical database. For each dataset, the distribution of physicochemical descriptors related to drug-likeness is presented. From these results, updated guidelines to prioritize compounds for targeting protein kinases are proposed. The results of a principal component analysis (PCA) show that the PKIDB dataset is fully encompassed within all PKIs found in the public database. This observation is reinforced by a principal moments of inertia (PMI) analysis of all molecules. Interestingly, we notice that PKIs in clinical trials tend to explore new 3D chemical space. While a great majority of PKIs is located on the area of “flatland”, we find few compounds exploring the 3D structural space. Finally, a scaffold diversity analysis of the two datasets, based on frequency counts was performed. The results give insight into the chemical space of PKIs, and can guide researchers to reach out new unexplored areas. PKIDB is freely accessible from the following website: http://www.icoa.fr/pkidb.
Production of a Distilled Spirit Using Cassava Flour as Raw Material: Chemical Characterization and Sensory Profile
Authors: Coelho Eduardo , Ballesteros Lina F. , Domingues Lucília , Vilanova Mar , Teixeira José A.
Published: July 2020

Cassava plays a key role in the food production and economies of several countries worldwide. Due to its starch content, alcoholic fermentation is a promising transformation process for adding value to cassava. However, most of the existing cassava beverages are from traditional origin, with the yields and quality often poorly known or controlled due to the use of artisanal production processes. This work aims at the application of easily implementable biotechnological tools for the production of cassava spirits, in order to add value to this raw material. Cassava flour was liquefied and saccharified using enzymatic cocktails, generating a fermentable broth with ~184 g L−1 of fermentable sugars. This was then fermented into an alcoholic product with ~10% ethanol by volume and distilled for spirit production. Cassava spirits with 40% ethanol by volume, with or without application of oak wood, were produced. For further valorization, volatile fractions of cassava spirits were characterized by gas chromatography–flame ionization detection (GC-FID) and GC–MS. These showed a predominance of yeast fermentation metabolites, complemented by wood extractives where oak chips were applied. Both produced spirits showed desirable sensory traits, receiving good acceptance by experienced tasters, demonstrating the feasibility of the proposed process to add value to cassava surplus.
Propofol Improved Glucose Tolerance Associated with Increased FGF-21 and GLP-1 Production in Male Sprague-Dawley Rats
Authors: Wu Chih-Cheng , Hung Chih-Jen , Wang Ya-Yu , Lin Shih-Yi , Chen Wen-Ying , Kuan Yu-Hsiang , Liao Su-Lan , Yang Ching-Ping , Chen Chun-Jung
Published: July 2020

Anesthetics, particularly volatile anesthetics, have been shown to impair glucose metabolism and cause hyperglycemia, closely linking them with mortality and morbidity as related to surgery. Beyond being an anesthetic used for general anesthesia and sedation, intravenous hypnotic propofol displays an effect on glucose metabolism. To extend the scope of propofol studies, its effects on glucose metabolism were evaluated in male Sprague-Dawley rats of various ages. Unlike chloral hydrate and isoflurane, propofol had little effect on basal glucose levels in rats at 2 months of age, although it did reduce chloral hydrate- and isoflurane-induced hyperglycemia. Propofol reduced postload glucose levels after either intraperitoneal or oral administration of glucose in both 7- and 12-month-old rats, but not those at 2 months of age. These improved effects regarding propofol on glucose metabolism were accompanied by an increase in insulin, fibroblast growth factor-21 (FGF-21), and glucagon-like peptide-1 (GLP-1) secretion. Additionally, an increase in hepatic FGF-21 expression, GLP-1 signaling, and FGF-21 signaling, along with a decrease in endoplasmic reticulum (ER) stress, were noted in propofol-treated rats at 7 months of age. Current findings imply that propofol may turn into insulin-sensitizing molecules during situations of existing insulin resistance, which involve FGF-21, GLP-1, and ER stress.
Aronia melanocarpa Fruits as a Rich Dietary Source of Chlorogenic Acids and Anthocyanins: 1H-NMR, HPLC-DAD, and Chemometric Studies
Authors: Zielińska Agnieszka , Siudem Paweł , Paradowska Katarzyna , Gralec Małgorzata , Kaźmierski Sławomir , Wawer Iwona
Published: July 2020

Aronia melanocarpa (Michx.) Elliott’s (chokeberry) besides anthocyanins contains significant amounts of hydroxycinnamic acids: Chlorogenic and its isomer neochlorogenic acid. They exhibit antioxidant, anti-inflammatory, antidiabetic, and antibacterial activities, thus they can have a significant impact on the health-promoting properties of Aronia. The aim of our research was to determine the changes in the content of chlorogenic acids (CGAs) and anthocyanins during fruit development and ripening, with a particular emphasis on acids. Aronia fruit samples were collected from July to October on two organic farms in Poland. The chemical composition of the extracts was determined by NMR spectroscopy and HPLC-DAD. 1H-NMR and HPLC data were analyzed using chemometric analysis and multivariate statistics (PCA). The results showed that the content of chlorogenic acids and anthocyanins changes during ripening and depends on the time of harvest and the region of cultivation. A correlation between the time of CGAs reduction and the appearance of anthocyanins was also noticed. The result of our research was also a database in the form of NMR parameters, which allows analysis of the metabolite profile and tracking of its changes. The 1H-NMR spectrum showing anthocyanin and CGA resonance can be considered the Aronia berry fingerprint.
Bio-Based Thermoplastic Starch Composites Reinforced by Dialdehyde Lignocellulose
Authors: Yin Peng , Zhou Wen , Zhang Xin , Guo Bin , Li Panxin
Published: July 2020

In order to improve the mechanical properties and water resistance of thermoplastic starch (TPS), a novel reinforcement of dialdehyde lignocellulose (DLC) was prepared via the oxidation of lignocellulose (LC) using sodium periodate. Then, the DLC-reinforced TPS composites were prepared by an extrusion and injection process using glycerol as a plasticizer. The DLC and LC were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and the effects of DLC content on the properties of the DLC/TPS composites were investigated via the evaluation of SEM images, mechanical properties, thermal stability, and contact angles. XRD showed that the crystallinity of the DLC decreased due to oxidation damage to the LC. SEM showed good dispersion of the DLC in the continuous TPS phase at low amounts of DLC, which related to good mechanical properties. The tensile strength of the DLC/TPS composite reached a maximum at a DLC content of 3 wt.%, while the elongation at break of the DLC/TPS composites increased with increasing DLC content. The DLC/TPS composites had better thermal stability than the neat TPS. As the DLC content increased, the water resistance first increased, then decreased. The highest tensile strength and elongation at break reached 5.26 MPa and 111.25%, respectively, and the highest contact angle was about 90.7°.
Study on Effect of Extraction Techniques and Seed Coat on Proteomic Distribution and Cheese Production from Soybean Milk
Authors: Al-Saedi Nadia , Agarwal Manjree , Ma Wujun , Islam Shahidul , Ren Yonglin
Published: July 2020

Soybean-based food products are a major source of protein. In the present study, proteins in soybean milk from seeds of the cultivar Bunya (Glycine max) were extracted using the cheesecloth and the centrifuge methods. The milk was produced through mechanical crushing of both whole and split seeds in water. Following separation by either the cheesecloth or centrifuge, proteins were isolated from the soybean milk by using thiourea/urea solubilisation and then separated them using two-dimensional polyacrylamide gel electrophoresis. The isolated proteins were identified by mass spectrometry. A total of 97 spots were identified including 49 that displayed different abundances. Of the two separation techniques, centrifuge separation gave higher protein extraction and more intense protein spots than cheesecloth separation. Eleven of the β-subunits of β-conglycinin, three of the α-subunits of β-conglycinin, and four of the mutant glycinin showed different levels of abundances between separation techniques, which might be related to subsequent cheese quality. Notably, split-seed soybean milk has less allergenic proteins with four α-subunits of β-conglycinin compared to whole-seed milk with eight of those proteins. The sensory evaluation showed that the cheese produced from split-soybean milk received higher consumer preferences compared to that of whole seed, which could be explained by their proteomic differences. The demonstrated reference map for whole and split-seed soybean milk could be further utilized in the research related to soybean cheesemaking.
Involvement of Integrin-Activating Peptides Derived from Tenascin-C in Cancer Aggression and New Anticancer Strategy Using the Fibronectin-Derived Integrin-Inactivating Peptide
Authors: Fujita Motomichi , Sasada Manabu , Iyoda Takuya , Fukai Fumio
Published: July 2020

Matricellular proteins, which exist in association with the extracellular matrix (ECM) and ECM protein molecules, harbor functional sites within their molecular structures. These functional sites are released through proteolytic cleavage by inflammatory proteinases, such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the peptides containing these functional sites have unique biological activities that are often not detected in the parent molecules. We previously showed that tenascin-C (TNC) and plasma fibronectin (pFN), examples of matricellular proteins, have cryptic bioactive sites that have opposite effects on cell adhesion to the ECM. A peptide containing the bioactive site of TNC, termed TNIIIA2, which is highly released at sites of inflammation and in the tumor microenvironment (TME), has the ability to potently and persistently activate β1-integrins. In the opposite manner, the peptide FNIII14 containing the bioactive site of pFN has the ability to inactivate β1-integrins. This review highlights that peptide TNIIIA2 can act as a procancer factor and peptide FNIII14 can act as an anticancer agent, based on the regulation on β1-integrin activation. Notably, the detrimental effects of TNIIIA2 can be inhibited by FNIII14. These findings open the possibility for new therapeutic strategies based on the inactivation of β1-integrin by FNIII14.
Stabilization of the Highly Hydrophobic Membrane Protein, Cytochrome bd Oxidase, on Metallic Surfaces for Direct Electrochemical Studies
Authors: Nikolaev Anton , Makarchuk Iryna , Thesseling Alexander , Hoeser Jo , Friedrich Thorsten , Melin Frédéric , Hellwig Petra
Published: July 2020

The cytochrome bd oxidase catalyzes the reduction of oxygen to water in bacteria and it is thus an interesting target for electrocatalytic studies and biosensor applications. The bd oxidase is completely embedded in the phospholipid membrane. In this study, the variation of the surface charge of thiol-modified gold nanoparticles, the length of the thiols and the other crucial parameters including optimal phospholipid content and type, have been performed, giving insight into the role of these factors for the optimal interaction and direct electron transfer of an integral membrane protein. Importantly, all three tested factors, the lipid type, the electrode surface charge and the thiol length mutually influenced the stability of films of the cytochrome bd oxidase. The best electrocatalytic responses were obtained on the neutral gold surface when the negatively charged phosphatidylglycerol (PG) was used and on the charged gold surface when the zwitterionic phosphatidylethanolamine (PE) was used. The advantages of the covalent binding of the membrane protein to the electrode surface over the non-covalent binding are also discussed.
Synthesis of Triazole-Linked SAM-Adenosine Conjugates: Functionalization of Adenosine at N-1 or N-6 Position without Protecting Groups
Authors: Atdjian Colette , Coelho Dylan , Iannazzo Laura , Ethève-Quelquejeu Mélanie , Braud Emmanuelle
Published: July 2020

More than 150 RNA chemical modifications have been identified to date. Among them, methylation of adenosine at the N-6 position (m6A) is crucial for RNA metabolism, stability and other important biological events. In particular, this is the most abundant mark found in mRNA in mammalian cells. The presence of a methyl group at the N-1 position of adenosine (m1A) is mostly found in ncRNA and mRNA and is mainly responsible for stability and translation fidelity. These modifications are installed by m6A and m1A RNA methyltransferases (RNA MTases), respectively. In human, deregulation of m6A RNA MTases activity is associated with many diseases including cancer. To date, the molecular mechanism involved in the methyl transfer, in particular substrate recognition, remains unclear. We report the synthesis of new SAM-adenosine conjugates containing a triazole linker branched at the N-1 or N-6 position of adenosine. Our methodology does not require protecting groups for the functionalization of adenosine at these two positions. The molecules described here were designed as potential bisubstrate analogues for m6A and m1A RNA MTases that could be further employed for structural studies. This is the first report of compounds mimicking the transition state of the methylation reaction catalyzed by m1A RNA MTases.
Continuous Flow Synthesis of Heterocycles: A Recent Update on the Flow Synthesis of Indoles
Authors: Colella Marco , Degennaro Leonardo , Luisi Renzo
Published: July 2020

Indole derivatives are among the most useful and interesting heterocycles employed in drug discovery and medicinal chemistry. In addition, flow chemistry and flow technology are changing the synthetic paradigm in the field of modern synthesis. In this review, the role of flow technology in the preparation of indole derivatives is showcased. Selected examples have been described with the aim to provide readers with an overview on the tactics and technologies used for targeting indole scaffolds.
Grouping, Spectrum–Effect Relationship and Antioxidant Compounds of Chinese Propolis from Different Regions Using Multivariate Analyses and Off-Line Anti-DPPH Assay
Authors: Jiang Xiasen , Tao Linchen , Li Chunguang , You Mengmeng , Li George Q. , Zhang Cuiping , Hu Fuliang
Published: July 2020

49 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic acid (TPC) and antioxidant activity. High-performance liquid chromatography (HPLC) analysis identified 15 common components, including key marker compounds pinocembrin, 3-O-acetylpinobanksin, galangin, chrysin, benzyl p-coumarate, pinobanksin and caffeic acid phenethyl ester (CAPE). Cluster analysis (CA) and correlation coefficients (CC) analysis showed that these propolis could be divided into three distinct groups. Principal component analysis (PCA) and multiple linear regression analysis (MLRA) revealed that the contents of isoferulic acid, caffeic acid, CAPE, 3,4-dimethoxycinnamic acid, chrysin and apigenin are closely related to the antioxidant properties of propolis. In addition, eight peak areas decreased after reacting with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals, indicating that these compounds have antioxidant activity. The results indicate that the grouping and spectrum–effect relationship of Chinese propolis are related to their chemical compositions, and several compounds may serve as a better marker for the antioxidant activity of Chinese propolis than TFC and TPC. The findings may help to develop better methods to evaluate the quality of propolis from different geographic origins.
In Vivo Biosynthesis of Inorganic Nanomaterials Using Eukaryotes—A Review
Authors: Rahman Ashiqur , Lin Julia , Jaramillo Francisco E. , Bazylinski Dennis A. , Jeffryes Clayton , Dahoumane Si Amar
Published: July 2020

Bionanotechnology, the use of biological resources to produce novel, valuable nanomaterials, has witnessed tremendous developments over the past two decades. This eco-friendly and sustainable approach enables the synthesis of numerous, diverse types of useful nanomaterials for many medical, commercial, and scientific applications. Countless reviews describing the biosynthesis of nanomaterials have been published. However, to the best of our knowledge, no review has been exclusively focused on the in vivo biosynthesis of inorganic nanomaterials. Therefore, the present review is dedicated to filling this gap by describing the many different facets of the in vivo biosynthesis of nanoparticles (NPs) using living eukaryotic cells and organisms—more specifically, live plants and living biomass of several species of microalgae, yeast, fungus, mammalian cells, and animals. It also highlights the strengths and weaknesses of the synthesis methodologies and the NP characteristics, bio-applications, and proposed synthesis mechanisms. This comprehensive review also brings attention to enabling a better understanding between the living organisms themselves and the synthesis conditions that allow their exploitation as nanobiotechnological production platforms as these might serve as a robust resource to boost and expand the bio-production and use of desirable, functional inorganic nanomaterials.