bluuebunny/crossref_metadata_2025 huggingface dataset:
Amidoxime Functionalization of Algal/Polyethyleneimine Beads for the Sorption of Sr(II) from Aqueous Solutions
Authors: Wei Yuezhou , Salih Khalid A. M. , Lu Siming , Hamza Mohammed F. , Fujita Toyohisa , Vincent Thierry , Guibal Eric
Published: October 2019

There is a need for developing new sorbents that incorporate renewable resources for the treatment of metal-containing solutions. Algal-polyethyleneimine beads (APEI) (reinforced with alginate) are functionalized by grafting amidoxime groups (AO-APEI). Physicochemical characteristics of the new material are characterized using FTIR, XPS, TGA, SEM, SEM-EDX, and BET. AO-APEI beads are tested for the recovery of Sr(II) from synthetic solutions after pH optimization (≈ pH 6). Uptake kinetics is fast (equilibrium ≈ 60–90 min). Sorption isotherm (fitted by the Langmuir equation) shows remarkable sorption capacity (≈ 189 mg Sr g−1). Sr(II) is desorbed using 0.2 M HCl/0.5 M CaCl2 solution; sorbent recycling over five cycles shows high stability in terms of sorption/desorption performances. The presence of competitor cations is studied in relation to the pH; the selectivity for Sr(II) is correlated to the softness parameter. Finally, the recovery of Sr(II) is carried out in complex solutions (seawater samples): AO-APEI is remarkably selective over highly concentrated metal cations such as Na(I), K(I), Mg(II), and Ca(II), with weaker selectivity over B(I) and As(V). AO-APEI appears to be a promising material for selective recovery of strontium from complex solutions (including seawater).
Synthesis and Characterization of N-Methyl Fatty Hydroxamic Acids from Ketapang Seed Oil Catalyzed by Lipase
Authors: Suhendra Dedy , Ryantin Gunawan Erin , Hajidi Hajidi
Published: October 2019

N-methyl fatty hydroxamic acid (N-MFHA), which is a derivative of hydroxamic acid (HA), was synthesized from ketapang seed oil (Terminalia catappa L.). In general, HAs have wide applications due to their chelating properties and biological activities. N-MFHAs were synthesized using immobilized lipase (Lipozyme TL IM) in biphasic medium which was the ketapang seed oil dissolved in hexane and N-methylhydroxylamine dissolved in water. The products were characterized through color testing and FT-IR spectroscopy after purification. Various factors affecting the enzyme activity investigated in the study included the effect of incubation time, the amount of lipase used, and the temperature. On the basis of the results, the optimum conditions for the synthesis of N-MFHA obtained are 25 h of incubation time, a temperature of 40 °C, and a ratio of 1:100 for the amount of enzyme (g)/oil (g). At the optimum conditions of the reaction, 59.7% of the oils were converted to N-MFHA.
Theoretical Study of the Effect of Different π Bridges Including an Azomethine Group in Triphenylamine-Based Dye for Dye-Sensitized Solar Cells
Authors: Delgado-Montiel Tomás , Soto-Rojo Rody , Baldenebro-López Jesús , Glossman-Mitnik Daniel
Published: October 2019

Ten molecules were theoretically calculated and studied through density functional theory with the M06 density functional and the 6-31G(d) basis set. The molecular systems have potential applications as sensitizers for dye-sensitized solar cells. Three molecules were taken from the literature, and seven are proposals inspired in the above, including the azomethine group in the π-bridge expecting a better charge transfer. These molecular structures are composed of triphenylamine (donor part); different combinations of azomethine, thiophene, and benzene derivatives (π-bridge); and cyanoacrylic acid (acceptor part). This study focused on the effect that the azomethine group caused on the π-bridge. Ground-state geometry optimization, the highest occupied molecular orbital, the lowest unoccupied molecular orbital, and their energy levels were obtained and analyzed. Absorption wavelengths, oscillator strengths, and electron transitions were obtained via time-dependent density functional theory using the M06-2X density functional and the 6-31G(d) basis set. The free energy of electron injection (ΔGinj) was calculated and analyzed. As an important part of this study, chemical reactivity parameters are discussed, such as chemical hardness, electrodonating power, electroaccepting power, and electrophilicity index. In conclusion, the inclusion of azomethine in the π-bridge improved the charge transfer and the electronic properties of triphenylamine-based dyes.
Antioxidant, Xanthine Oxidase, α-Amylase and α-Glucosidase Inhibitory Activities of Bioactive Compounds from Rumex crispus L. Root
Authors: Minh Truong Ngoc , Van Truong Mai , Andriana Yusuf , Vinh Le The , Hau Dang Viet , Duyen Dang Hong , Guzman-Gelani Chona de
Published: October 2019

The root of Rumex crispus L. has been shown to possess anti-gout and anti-diabetic properties, but the compounds responsible for these pharmaceutical effects have not yet been reported. In this study, we aimed to isolate and purify active components from the root of R. crispus, and to evaluate their anti-radical, anti-gout and anti-diabetic capacities. From the ethyl acetate (EtOAc) extract, two compounds, chrysophanol (1) and physcion (2), were isolated by column chromatography with an elution of hexane and EtOAc at a 9:1 ratio. Their structures were identified by spectrometric techniques including gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), X-ray diffraction analyses and nuclear magnetic resonance (NMR). The results of bioassays indicated that (1) showed stronger activities than (2). For antioxidant activity, (1) and (2) exhibited remarkable DPPH radical scavenging capacity (IC50 = 9.8 and 12.1 µg/mL), which was about two times stronger than BHT (IC50 = 19.4 µg/mL). The anti-gout property of (1) and (2) were comparable to the positive control allopurinol, these compounds exerted strong inhibition against the activity of xanthine oxidase (IC50 = 36.4 and 45.0 µg/mL, respectively). In the anti-diabetic assay, (1) and (2) displayed considerable inhibitory ability on α-glucosidase, their IC50 values (IC50 = 20.1 and 18.9 µg/mL, respectively) were higher than that of standard acarbose (IC50 = 143.4 µg/mL). Findings of this study highlight that (1) and (2) may be promising agents to treat gout and diabetes, which may greatly contribute to the medicinal properties of Rumex crispus root.
Aromatic vs. Aliphatic Hyperbranched Polyphosphoesters as Flame Retardants in Epoxy Resins
Authors: Markwart Jens C. , Battig Alexander , Velencoso Maria M. , Pollok Dennis , Schartel Bernhard , Wurm Frederik R.
Published: October 2019

The current trend for future flame retardants (FRs) goes to novel efficient halogen-free materials, due to the ban of several halogenated FRs. Among the most promising alternatives are phosphorus-based FRs, and of those, polymeric materials with complex shape have been recently reported. Herein, we present novel halogen-free aromatic and aliphatic hyperbranched polyphosphoesters (hbPPEs), which were synthesized by olefin metathesis polymerization and investigated them as a FR in epoxy resins. We compare their efficiency (aliphatic vs. aromatic) and further assess the differences between the monomeric compounds and the hbPPEs. The decomposition and vaporizing behavior of a compound is an important factor in its flame-retardant behavior, but also the interaction with the pyrolyzing matrix has a significant influence on the performance. Therefore, the challenge in designing a FR is to optimize the chemical structure and its decomposition pathway to the matrix, with regards to time and temperature. This behavior becomes obvious in this study, and explains the superior gas phase activity of the aliphatic FRs.
Protein Prenylation in Plant Stress Responses
Authors: Hála Michal , Žárský Viktor
Published: October 2019

Protein prenylation is one of the most important posttranslational modifications of proteins. Prenylated proteins play important roles in different developmental processes as well as stress responses in plants as the addition of hydrophobic prenyl chains (mostly farnesyl or geranyl) allow otherwise hydrophilic proteins to operate as peripheral lipid membrane proteins. This review focuses on selected aspects connecting protein prenylation with plant responses to both abiotic and biotic stresses. It summarizes how changes in protein prenylation impact plant growth, deals with several families of proteins involved in stress response and highlights prominent regulatory importance of prenylated small GTPases and chaperons. Potential possibilities of these proteins to be applicable for biotechnologies are discussed.
Guanidine-Containing Polyhydroxyl Macrolides: Chemistry, Biology, and Structure-Activity Relationship
Authors: Song Xiaoyuan , Yuan Ganjun , Li Peibo , Cao Sheng
Published: October 2019

Antimicrobial resistance has been seriously threatening human health, and discovering new antimicrobial agents from the natural resource is still an important pathway among various strategies to prevent resistance. Guanidine-containing polyhydroxyl macrolides, containing a polyhydroxyl lactone ring and a guanidyl side chain, can be produced by many actinomycetes and have been proved to possess many bioactivities, especially broad-spectrum antibacterial and antifungal activities. To explore the potential of these compounds to be developed into new antimicrobial agents, a review on their structural diversities, spectroscopic characterizations, bioactivities, acute toxicities, antimicrobial mechanisms, and the structure-activity relationship was first performed based on the summaries and analyses of related publications from 1959 to 2019. A total of 63 guanidine-containing polyhydroxyl macrolides were reported, including 46 prototype compounds isolated from 33 marine and terrestrial actinomycetes and 17 structural derivatives. Combining with their antimicrobial mechanisms, structure-activity relationship analyses indicated that the terminal guanidine group and lactone ring of these compounds are vital for their antibacterial and antifungal activities. Further, based on their bioactivities and toxicity analyses, the discovery of guanidyl side-chain targeting to lipoteichoic acid of Staphylococcus aureus indicated that these compounds have a great potency to be developed into antimicrobial and anti-inflammatory drugs.
Optimization of Laccase from Ganoderma lucidum Decolorizing Remazol Brilliant Blue R and Glac1 as Main Laccase-Contributing Gene
Authors: Qin Peng , Wu Yuetong , Adil Bilal , Wang Jie , Gu Yunfu , Yu Xiumei , Zhao Ke , Zhang Xiaoping , Ma Menggen , Chen Qiang , Chen Xiaoqiong , Zhang Zongjin , Xiang Quanju
Published: October 2019

Many dyes and pigments are used in textile and printing industries, and their wastewater has been classed as a top source of pollution. Biodegradation of dyes by fungal laccase has great potential. In this work, the influence of reaction time, pH, temperature, dye concentration, metal ions, and mediators on laccase-catalyzed Remazol Brilliant Blue R dye (RBBR) decolorization were investigated in vitro using crude laccase from the white-rot fungus Ganoderma lucidum. The optimal decolorization percentage (50.3%) was achieved at 35 °C, pH 4.0, and 200 ppm RBBR in 30 min. The mediator effects from syringaldehyde, 1-hydroxybenzotriazole, and vanillin were compared, and 0.1 mM vanillin was found to obviously increase the decolorization percentage of RBBR to 98.7%. Laccase-mediated decolorization percentages significantly increased in the presence of 5 mM Na+ and Cu2+, and decolorization percentages reached 62.4% and 62.2%, respectively. Real-time fluorescence-quantitative PCR (RT-PCR) and protein mass spectrometry results showed that among the 15 laccase isoenzyme genes, Glac1 was the main laccase-contributing gene, contributing the most to the laccase enzyme activity and decolorization process. These results also indicate that under optimal conditions, G. lucidum laccases, especially Glac1, have a strong potential to remove RBBR from reactive dye effluent.
Cloning and Characterization of a Cold-adapted Chitosanase from Marine Bacterium Bacillus sp. BY01
Authors: Yang Yue , Zheng Zhou , Xiao Yifei , Zhang Jiaojiao , Zhou Yu , Li Xiao , Li Shangyong , Yu Huiqing
Published: October 2019

Chitosanase plays an important role in the production of chitooligosaccharides (CHOS), which possess various biological activities. Herein, a glycoside hydrolase (GH) family 46 chitosanase-encoding gene, csnB, was cloned from marine bacterium Bacillus sp. BY01 and heterologously expressed in Escherichia coli. The recombinant chitosanase, CsnB, was optimally active at 35 °C and pH 5.0. It was also revealed to be a cold-adapted enzyme, maintaining 39.5% and 40.4% of its maximum activity at 0 and 10 °C, respectively. Meanwhile, CsnB showed wide pH-stability within the range of pH 3.0 to 7.0. Then, an improved reaction condition was built to enhance its thermostability with a final glycerol volume concentration of 20%. Moreover, CsnB was determined to be an endo-type chitosanase, yielding chitosan disaccharides and trisaccharides as the main products. Overall, CsnB provides a new choice for enzymatic CHOS production.
Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides
Authors: Yadav Yogesh , Sharma Deepti , Kaushik Kumar , Kumar Vineet , Jha Amitabh , Prasad Ashok K. , Len Christophe , Malhotra Sanjay V. , Wengel Jesper , Parmar Virinder S.
Published: October 2019

The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI50 9.3 µM) and breast cancer cell line HS 578T (GI50 3.0 µM).
Synthesis, Spectroscopy and Electrochemistry in Relation to DFT Computed Energies of Ferrocene- and Ruthenocene-Containing β-Diketonato Iridium(III) Heteroleptic Complexes. Structure of [(2-Pyridylphenyl)2Ir(RcCOCHCOCH3]
Authors: Buitendach Blenerhassitt E. , Conradie Jeanet , Malan Frederick P. , Niemantsverdriet J. W. (Hans) , Swarts Jannie C.
Published: October 2019

A series of new ferrocene- and ruthenocene-containing iridium(III) heteroleptic complexes of the type [(ppy)2Ir(RCOCHCOR′)], with ppy = 2-pyridylphenyl, R = Fc = FeII(η5-C5H4)(η5-C5H5) and R′ = CH3 (1) or Fc (2), as well as R = Rc = RuII(η5-C5H4)(η5-C5H5) and R′ = CH3 (3), Rc (4) or Fc (5) was synthesized via the reaction of appropriate metallocene-containing β-diketonato ligands with [(ppy)2(μ-Cl)Ir]2. The single crystal structure of 3 (monoclinic, P21/n, Z = 4) is described. Complexes 1–5 absorb light strongly in the region 280−480 nm the metallocenyl β-diketonato substituents quench phosphorescence in 1–5. Cyclic and square wave voltammetric studies in CH2Cl2/[N(nBu)4][B(C6F5)4] allowed observation of a reversible IrIII/IV redox couple as well as well-resolved ferrocenyl (Fc) and ruthenocenyl (Rc) one-electron transfer steps in 1−5. The sequence of redox events is in the order Fc oxidation, then IrIII oxidation and finally ruthenocene oxidation, all in one-electron transfer steps. Generation of IrIV quenched phosphorescence in 6, [(ppy)2Ir(H3CCOCHCOCH3)]. This study made it possible to predict the IrIII/IV formal reduction potential from Gordy scale group electronegativities, χR and/or ΣχR′ of β-diketonato pendent side groups as well as from DFT-calculated energies of the highest occupied molecular orbital of the species involved in the IrIII/IV oxidation at a 98% accuracy level.
ATR-FTIR Spectroscopy, a New Non-Destructive Approach for the Quantitative Determination of Biogenic Silica in Marine Sediments
Authors: Melucci Dora , Zappi Alessandro , Poggioli Francesca , Morozzi Pietro , Giglio Federico , Tositti Laura
Published: October 2019

Biogenic silica is the major component of the external skeleton of marine micro-organisms, such as diatoms, which, after the organisms death, settle down onto the seabed. These micro-organisms are involved in the CO2 cycle because they remove it from the atmosphere through photosynthesis. The biogenic silica content in marine sediments, therefore, is an indicator of primary productivity in present and past epochs, which is useful to study the CO2 trends. Quantification of biosilica in sediments is traditionally carried out by wet chemistry followed by spectrophotometry, a time-consuming analytical method that, besides being destructive, is affected by a strong risk of analytical biases owing to the dissolution of other silicatic components in the mineral matrix. In the present work, the biosilica content was directly evaluated in sediment samples, without chemically altering them, by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Quantification was performed by combining the multivariate standard addition method (MSAM) with the net analyte signal (NAS) procedure to solve the strong matrix effect of sediment samples. Twenty-one sediment samples from a sediment core and one reference standard sample were analyzed, and the results (extrapolated concentrations) were found to be comparable to those obtained by the traditional wet method, thus demonstrating the feasibility of the ATR-FTIR-MSAM-NAS approach as an alternative method for the quantification of biosilica. Future developments will cover in depth investigation on biosilica from other biogenic sources, the extension of the method to sediments of other provenance, and the use higher resolution IR spectrometers.
Bypass of the Major Alkylative DNA Lesion by Human DNA Polymerase η
Authors: Koag Myong-Chul , Jung Hunmin , Kou Yi , Lee Seongmin
Published: October 2019

A wide range of endogenous and exogenous alkylating agents attack DNA to generate various alkylation adducts. N7-methyl-2-deoxyguanosine (Fm7dG) is the most abundant alkylative DNA lesion. If not repaired, Fm7dG can undergo spontaneous depurination, imidazole ring-opening, or bypass by translesion synthesis DNA polymerases. Human DNA polymerase η (polη) efficiently catalyzes across Fm7dG in vitro, but its structural basis is unknown. Herein, we report a crystal structure of polη in complex with templating Fm7dG and an incoming nonhydrolyzable dCTP analog, where a 2′-fluorine-mediated transition destabilization approach was used to prevent the spontaneous depurination of Fm7dG. The structure showed that polη readily accommodated the Fm7dG:dCTP base pair with little conformational change of protein and DNA. In the catalytic site, Fm7dG and dCTP formed three hydrogen bonds with a Watson–Crick geometry, indicating that the major keto tautomer of Fm7dG is involved in base pairing. The polη-Fm7dG:dCTP structure was essentially identical to the corresponding undamaged structure, which explained the efficient bypass of the major methylated lesion. Overall, the first structure of translesion synthesis DNA polymerase bypassing Fm7dG suggests that in the catalytic site of Y-family DNA polymerases, small N7-alkylguanine adducts may be well tolerated and form the canonical Watson–Crick base pair with dCTP through their keto tautomers.
Quantitative Analyses of Nine Phenolic Compounds and Their Antioxidant Activities from Thirty-Seven Varieties of Raspberry Grown in the Qinghai-Tibetan Plateau Region
Authors: Wang Yuwei , Liang Jian , Luan Guangxiang , Zhang Shoude , Zhuoma Yixi , Xie Jiuxiang , Zhou Wu
Published: October 2019

In this work, an efficient method for the rapid extraction and separation of antioxidant phenols was developed and optimized. The method was then applied to extract and separate nine phenols from 37 varieties of raspberry, in which their antioxidant activities were further investigated. First, the extraction was conducted using ultra-sonication, which was then further separated using reversed-phase high-performance liquid chromatography/ultraviolet (RP-HPLC/UV) analysis. In this step, several key parameters (volume of the extraction reagent, time of extraction, and the temperature of extraction) affecting its efficiency were investigated and optimized using the response surface methodology (RSM) combined with the Box–Behnken design (BBD) so that the optimal conditions were obtained. According to the overall results of the optimization study, the optimal conditions were chosen as follows: volume of extraction reagent = 2.0 mL, time of extraction = 50.0 min, and temperature of extraction = 50 °C. The optimal conditions were then applied to extract nine phenols, including gallic acid, catechin, chlorogenic acid, vanillic acid, syringic acid, cumaric acid, ferulic acid, rosemary acid, and quercetin from 37 raspberry varieties. The extracted phenols were characterized and their antioxidant activities, including DPPH− and ABTS− free radical scavenging and intracellular reactive oxygen species (ROS) activity, using HepG2 cells as the model, were subsequently studied. The findings suggested that although their contents varied among most raspberry varieties, these phenols significantly contributed toward their antioxidant capacity and scavenging intracellular ROS activities. This study provides a scientific and theoretical basis for the selection of raspberry varieties and product development in Qinghai province.
Numerical Investigation on the Effects of Dielectric Barrier on a Nanosecond Pulsed Surface Dielectric Barrier Discharge
Authors: Zhang Shen , Chen Zhenli , Zhang Binqian , Chen Yingchun
Published: October 2019

In order to understand the impacts of dielectric barrier on the discharge characteristics of a nanosecond pulsed surface dielectric barrier discharge (NS-DBD), the effects of dielectric constant and dielectric barrier thickness are numerically investigated by using a three-equation drift–diffusion model with a 4-species 4-reaction air chemistry. When the dielectric constant increases, while the dielectric barrier thickness is fixed, the streamer propagation speed (V), the maximum streamer length (L), the discharge energy ( Q D _ e i ), and the gas heating ( Q G H ) of a pulse increase, but the plasma sheath thickness (h), the fast gas heating efficiency η , and the charge densities on the wall surface decrease. When the dielectric barrier thickness increases, while the dielectric constant is fixed, V, L, Q D _ e i , and Q G H of a pulse decrease, but h, η , and the charge densities on the wall surface increase. It can be concluded that the increase of the dielectric constant or the decrease of the dielectric barrier thickness results in the increase of the capacitance of the dielectric barrier, which enhances the discharge intensity. Increasing the dielectric constant and thinning the dielectric barrier layer improve the performance of the NS-DBD actuators.
Reaction of Papaverine with Baran DiversinatesTM
Authors: Egbewande Folake A. , Coster Mark J. , Jenkins Ian D. , Davis Rohan A.
Published: October 2019

The reaction of papaverine with a series of Baran DiversinatesTM is reported. Although the yields were low, it was possible to synthesize a small biodiscovery library using this plant alkaloid as a scaffold for late-stage C–H functionalization. Ten papaverine analogues (2–11), including seven new compounds, were synthesized. An unexpected radical-induced exchange reaction is reported where the dimethoxybenzyl group of papaverine was replaced by an alkyl group. This side reaction enabled the synthesis of additional novel fragments based on the isoquinoline scaffold, which is present in numerous natural products. Possible reasons for the poor yields in the DiversinateTM reactions with this particular scaffold are discussed.
Trends and Exceptions in the Interaction of Hydroxamic Acid Derivatives of Common Di- and Tripeptides with Some 3d and 4d Metal Ions in Aqueous Solution
Authors: Ozsváth András , Bíró Linda , Nagy Eszter Márta , Buglyó Péter , Sanna Daniele , Farkas Etelka
Published: October 2019

By using various techniques (pH-potentiometry, UV-Visible spectrophotometry, 1H and 17O-NMR, EPR, ESI-MS), first time in the literature, solution equilibrium study has been performed on complexes of dipeptide and tripeptide hydroxamic acids—AlaAlaNHOH, AlaAlaN(Me)OH, AlaGlyGlyNHOH, and AlaGlyGlyN(Me)OH—with 4d metals: the essential Mo(VI) and two half-sandwich type cations, [(η6-p-cym)Ru(H2O)3]2+ as well as [(η5-Cp*)Rh(H2O)3]2+, the latter two having potential importance in cancer therapy. The tripeptide derivatives have also been studied with some biologically important 3d metals, such as Fe(III), Ni(II), Cu(II), and Zn(II), in order to compare these new results with the corresponding previously obtained ones on dipeptide hydroxamic acids. Based on the outcomes, the effects of the type of metal ions, the coordination number, the number and types of donor atoms, and their relative positions to each other on the complexation have been evaluated in the present work. We hope that these collected results might be used when a new peptide-based hydroxamic acid molecule is planned with some purpose, e.g. to develop a potential metalloenzyme inhibitor.
A Chemometric Analysis of Deep-Sea Natural Products
Authors: Pilkington Lisa I.
Published: October 2019

Deep-sea natural products have been created by unique marine organisms that thrive in a challenging environment of extreme conditions for its inhabitants. In this study, 179 deep-sea natural products isolated from 2009 to 2013 were investigated by analysing their physicochemical properties that are important indicators of the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profile of a compound. The study and analysis of these molecular descriptors and characteristics enabled the defining of these compounds in various chemical spaces, particularly as an indication of their drug-likeness and position in chemical space and is the first to be conducted to analyse deep-sea derived natural products. It was found that ~40% of all deep-sea natural products were drug-like and 2/3 were within Known Drug Space (KDS), highlighting the high drug-likeness of a significant proportion of deep-sea natural products, most of which have already been shown to have notable biological activities, that should be further investigated as potential therapeutics. Furthermore, this study was able to reveal the general structural differences between compounds from Animalia, Bacteria and Fungi organisms where it was observed that natural products from members of the Animalia kingdom are structurally more varied than compounds from bacteria and fungi. It was also noted that, in general, fungi-derived compounds occupy a more favourable position in drug-like chemical space and are a rich and promising source of biologically-active natural products for the purposes of drug development and therapeutic application.
Kinesin Eg5 Targeting Inhibitors as a New Strategy for Gastric Adenocarcinoma Treatment
Authors: Marconi Guya Diletta , Carradori Simone , Ricci Alessia , Guglielmi Paolo , Cataldi Amelia , Zara Susi
Published: October 2019

The Kinesins are proteins involved in several biological processes such as mitosis, intracellular transport, and microtubule movement. The mitotic process is allowed by the correct formation of the mitotic spindle which consists of microtubules originating from the spindle poles. In recent years, kinesin Eg5 inhibitors were studied as new chemotherapeutic drugs, due to the lack of side effects and resistance mechanisms. The aim of this work was to investigate the molecular signaling underlying the administration of novel kinesis Eg5 inhibitors in an in vitro model of gastric adenocarcinoma. Data obtained from analogues of K858 led us to select compounds 2 and 41, due to their lower IC50 values. The ability of kinesin inhibitors to induce apoptosis was investigated by evaluating Bax and Caspase-3 protein expression, evidencing that compound 41 and K858 markedly raise Bax expression, while only compounds 2 and 41 co-administrated with K858 trigger Caspase-3 activation. The inhibition of mitotic spindle was measured by β-tubulin immunofluorescence analysis revealing monopolar spindles formation in gastric cancer cells treated with compounds 2, 41, and K858. Nitric Oxide Synthase (NOS-2) and Matrix Metalloproteinase 9 (MMP-9) expression levels were measured finding a NOS-2-mediated downregulation of MMP-9 when compound 41 and K858 are co-administered. However, this is in contrast to what was reported by migration assay in which both novel compounds and K858 in monotherapy markedly reduce cell migration. This work remarks the importance of understanding and exploring the biological effects of different novel Eg5 kinesin inhibitors administered in monotherapy and in combination with K858 as potential strategy to counteract gastric cancer.
Structure of Diferrocenyl Thioketone: From Molecule to Crystal
Authors: Matczak Piotr , Mlostoń Grzegorz , Hamera-Fałdyga Róża , Görls Helmar , Weigand Wolfgang
Published: October 2019

Ferrocenyl-functionalized thioketones have recently been recognized as useful building blocks for sulfur-containing compounds with potential applications in materials chemistry. This work is devoted to a single representative of such thioketones, namely diferrocenyl thioketone (Fc2CS), whose structure has been determined here for the first time. Both X-ray crystallography and a wide variety of quantum-chemical methods were used to explore the structure of Fc2CS. In addition to the X-ray structure determination, intermolecular interactions occurring in the crystal structure of Fc2CS were examined in detail by quantum-chemical methods. These methods were also an invaluable tool in studying the molecular structure of Fc2CS, from the gas phase to solutions and to its crystal. Intramolecular interactions governing the conformational behavior of an isolated Fc2CS molecule were deduced from quantum-chemical analyses carried out in orbital space and real space. Our experimental and theoretical results indicate that the main structural features of an isolated Fc2CS molecule in its lowest-energy geometry are retained both upon solvation and in the crystal. The tilt of ferrocenyl groups is only slightly affected by crystal packing forces that are dominated by dispersion. Nonetheless, a network of intermolecular interactions, such as H···H, C···H and S···H, was detected in the Fc2CS crystal but each of them is fairly weak.
Synthesis, Antitumor Activity, and Docking Analysis of New Pyrido[3′,2′:4,5]furo(thieno)[3,2-d]pyrimidin-8-amines
Authors: Sirakanyan Samvel N. , Spinelli Domenico , Geronikaki Athina , Hakobyan Elmira K. , Sahakyan Harutyun , Arabyan Erik , Zakaryan Hovakim , Nersesyan Lusine E. , Aharonyan Anahit S. , Danielyan Irina S. , Muradyan Rafayel E. , Hovakimyan Anush A.
Published: October 2019

Continuing our research in the field of new heterocyclic compounds, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3′,2′:4,5](furo)thieno[3,2-d]pyrimidines as well as of two new heterocyclic systems: furo[2–e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine. Thus, by refluxing the 8-chloro derivatives of pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidines with various amines, the relevant pyrido[3′,2′:4,5]thieno(furo)[3,2-d]pyrimidin-8-amines were obtained. Further, the cyclization of some amines under the action of phosphorus oxychloride led to the formation of new heterorings: imidazo[1,2-c]pyrimidine and pyrimido[1,2-c]pyrimidine. The possible antitumor activity of the newly synthesized compounds was evaluated in vitro. The biological tests evidenced that some of them showed pronounced antitumor activity. A study of the structure–activity relationships revealed that the compound activity depended mostly on the nature of the amine fragments. A docking analysis was also performed for the most active compounds.
β-Cyclodextrin Assisted Liquid–Liquid Microextraction Based on Solidification of the Floating Organic Droplets Method for Determination of Neonicotinoid Residues
Authors: Vichapong Jitlada , Moyakao Khwankaew , Kachangoon Rawikan , Burakham Rodjana , Santaladchaiyakit Yanawath , Srijaranai Supalax
Published: October 2019

An efficient and environment-friendly microextraction method, namely, β-cyclodextrin assisted liquid–liquid microextraction, based on solidification of the floating organic droplets method coupled with HPLC is investigated for the sensitive determination of trace neonicotinoid pesticide residues. In this method, β-cyclodextrin is used as a disperser solvent, while 1-octanol is selected as an extraction solvent. β-cyclodextrins was found to decrease interfacial tension and increase the contact area between the organic and water phases with the help of centrifugation. A cloudy solution was rapidly formed and then centrifuged to complete phase separation. Various key parameters influencing extraction efficiency were systematically investigated and optimized; they include salt addition, concentration of β-cyclodextrin, and volume of extraction solvent (1-octanol). Under optimum conditions, good linearity was obtained with coefficient for determination (R2) greater than 0.99. A low limit of detection, high enrichment factor, and good recovery (83 – 132) were achieved. This proves that the proposed method can be applied to determine trace neonicotinoid pesticide residues in natural surface water samples.
Prediction of Severity of Drug-Drug Interactions Caused by Enzyme Inhibition and Activation
Authors: Dmitriev Alexander , Filimonov Dmitry , Lagunin Alexey , Karasev Dmitry , Pogodin Pavel , Rudik Anastasiya , Poroikov Vladimir
Published: October 2019

Drug-drug interactions (DDIs) severity assessment is a crucial problem because polypharmacy is increasingly common in modern medical practice. Many DDIs are caused by alterations of the plasma concentrations of one drug due to another drug inhibiting and/or inducing the metabolism or transporter-mediated disposition of the victim drug. Accurate assessment of clinically relevant DDIs for novel drug candidates represents one of the significant tasks of contemporary drug research and development and is important for practicing physicians. This work is a development of our previous investigations and aimed to create a model for the severity of DDIs prediction. PASS program and PoSMNA descriptors were implemented for prediction of all five classes of DDIs severity according to OpeRational ClassificAtion (ORCA) system: contraindicated (class 1), provisionally contraindicated (class 2), conditional (class 3), minimal risk (class 4), no interaction (class 5). Prediction can be carried out both for known drugs and for new, not yet synthesized substances using only their structural formulas. Created model provides an assessment of DDIs severity by prediction of different ORCA classes from the first most dangerous class to the fifth class when DDIs do not take place in the human organism. The average accuracy of DDIs class prediction is about 0.75.
Synthesis and Chemiluminescent Properties of Amino-Acylated luminol Derivatives Bearing Phosphonium Cations
Authors: Pantelia Anna , Daskalaki Ira , Cuquerella M. Consuelo , Rotas Georgios , Miranda Miguel A. , Vougioukalakis Georgios C.
Published: October 2019

The monitoring of reactive oxygen species in living cells provides valuable information on cell function and performance. Lately, the development of chemiluminescence-based reactive oxygen species monitoring has gained increased attention due to the advantages posed by chemiluminescence, including its rapid measurement and high sensitivity. In this respect, specific organelle-targeting trackers with strong chemiluminescence performance are of high importance. We herein report the synthesis and chemiluminescence properties of eight novel phosphonium-functionalized amino-acylated luminol and isoluminol derivatives, designed as mitochondriotropic chemiluminescence reactive oxygen species trackers. Three different phosphonium cationic moieties were employed (phenyl, p-tolyl, and cyclohexyl), as well as two alkanoyl chains (hexanoyl and undecanoyl) as bridges/linkers. Synthesis is accomplished via the acylation of the corresponding phthalimides, as phthalhydrazide precursors, followed by hydrazinolysis. This method was chosen because the direct acylation of (iso)luminol was discouraging. The new derivatives’ chemiluminescence was evaluated and compared with that of the parent molecules. A relatively poor chemiluminescence performance was observed for all derivatives, with the isoluminol-based ones being the poorest. This result is mainly attributed to the low yield of the fluorescence species formation during the chemiluminescence oxidation reaction.
Super Ductility of Nanoglass Aluminium Nitride
Authors: Zhao Yinbo , Peng Xianghe , Huang Cheng , Yang Bo , Hu Ning , Wang Mingchao
Published: October 2019

Ceramics have been widely used in many fields because of their distinctive properties, however, brittle fracture usually limits their application. To solve this problem, nanoglass ceramics were developed. In this article, we numerically investigated the mechanical properties of nanoglass aluminium nitride (ng-AlN) with different glassy grain sizes under tension using molecular dynamics simulations. It was found that ng-AlN exhibits super ductility and tends to deform uniformly without the formation of voids as the glassy grain size decreases to about 1 nm, which was attributed to a large number of uniformly distributed shear transformation zones (STZs). We further investigated the effects of temperature and strain rate on ng-AlNd = 1 nm, which showed that temperature insignificantly influences the elastic modulus, while the dependence of the ultimate strength on temperature follows the T2/3 scaling law. Meanwhile, the ultimate strength of ng-AlNd = 1 nm is positively correlated with the strain rate, following a power function relationship.
Mixed-Solvent Polarity-Assisted Phase Transition of Cesium Lead Halide Perovskite Nanocrystals with Improved Stability at Room Temperature
Authors: Yun Rui , Luo Li , He Jingqi , Wang Jiaxi , Li Xiaofen , Zhao Weiren , Nie Zhaogang , Lin Zhiping
Published: October 2019

Cesium lead halide perovskite nanocrystals (NCs) have attracted enormous interest in light-emitting diode, photodetector and low-threshold lasing application in terms of their unique optical and electrical performance. However, little attention has been paid to other structures associated with CsPbBr3, such as CsPb2Br5. Herein, we realize a facile method to prepare dual-phase NCs with improved stability against polar solvents by replacing conventional oleylamine with cetyltrimethyl ammonium bromide (CTAB) in the reprecipitation process. The growth of NCs can be regulated with different ratios of toluene and ethanol depending on solvent polarity, which not only obtains NCs with different sizes and morphologies, but also controls phase transition between orthorhombic CsPbBr3 and tetragonal CsPb2Br5. The photoluminescence (PL) and defect density calculated exhibit considerable solvent polarity dependence, which is ascribed to solvent polarity affecting the ability of CTAB to passivate surface defects and improve stoichiometry in the system. This new synthetic method of perovskite material will be helpful for further studies in the field of lighting and detectors.
Effects of Hybridized Organically Modified Montmorillonite and Cellulose Nanocrystals on Rheological Properties and Thermal Stability of K-Carrageenan Bio-Nanocomposite
Authors: Zakuwan Siti Zarina , Ahmad Ishak
Published: October 2019

Herein, hybrid k-carrageenan bio-nanocomposite films were fabricated by using two types of nanofillers, organically modified montmorillonite (OMMT), and cellulose nanocrystals (CNCs). Hybrid bio-nanocomposite films were made by casting techniques employing 4 wt% of CNCs, OMMT, and hybridized CNCs/OMMT in a 1:1 ratio. The rheological and morphological properties and thermal stability of all composites were investigated using rotational rheometry, thermogravimetry analysis, differential scanning calorimetry, field emission scanning electron microscopy, and transmission electron microscopy (TEM). The results showed that the hybrid CNC/OMMT bio-nanocomposite exhibited significantly improved properties as compared to those for the bio-nanocomposites with single fillers due to the nanosize and homogenous nanofiller dispersion in the matrix. Rheological analysis of the hybrid bio-nanocomposite showed higher dynamic shear storage modulus and complex viscosity values when compared to those for the bio-nanocomposite with individual fillers. The TEM analysis of the hybridized CNC/OMMT bio-nanocomposite revealed that more particles were packed together in the CNC network, which restricted the matrix mobility. The heat resistance and thermal stability bio-nanocomposite k-carrageenan film enhanced rapidly with the addition of hybridized CNCs/OMMT to 275 °C. The hybridized CNCs/OMMT exhibited synergistic effects due to the good affinity through interfacial interactions, resulting in the improvement of the material properties.
Alterations in IL-6/STAT3 Signaling by Korean Mistletoe Lectin Regulate the Self-Renewal Activity of Placenta-Derived Mesenchymal Stem Cells
Authors: Kim Gi Dae , Choi Jong Ho , Lim Seung Mook , Jun Ji Hye , Moon Ji Wook , Kim Gi Jin
Published: October 2019

Korean mistletoe (Viscum album L. var. coloratum) lectin (VCA) is known as an anticancer drug. However, it is not clear whether VCA affects the self-renewal activity of mesenchymal stem cells (MSCs). Therefore, the objectives of this study were to analyze the effect of VCA on the proliferation of MSCs and expression of stemness markers. We also evaluated the usefulness of placenta-derived MSCs (PD-MSCs) as a screening tool. VCA was stably administered to MSCs, and analyzed self-renewal activities. The effect of IL-6 signaling on MSC proliferation was explored by quantitative methylation-specific PCR (qMSP) and western blot analysis. Compared with the control condition, low concentrations of VCA (10 pg/mL) induced an increase in the self-renewal activity of MSCs. Interestingly, a low concentration of VCA promoted IL-6 signaling in PD-MSCs through altered IL-6/STAT3 gene methylation. Furthermore, inhibition of IL-6 expression in PD-MSCs using an anti-IL-6 antibody caused a decrease in their self-renewal activity through IL-6/STAT3 signaling by altering IL-6/STAT3 gene methylation. These findings provide helpful data for understanding the mechanism of MSC self-renewal via VCA and show that VCA may be useful as a functional natural product for developing efficient therapies using placenta-derived stem cells.
The Current Status of Cytomegalovirus (CMV) Prevalence in the MENA Region: A Systematic Review
Authors: Al Mana Hassan , Yassine Hadi M. , Younes Nadin N. , Al-Mohannadi Anjud , Al-Sadeq Duaa W. , Alhababi Dalal , Nasser Elham A. , Nasrallah Gheyath K.
Published: October 2019

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus worldwide. According to the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), CMV infects people of all ages, and by the age of five, approximately one-third of children in the United States are infected. Although the infection is generally asymptomatic, it can cause severe disease in immunocompromised patients, transplant and transfusion recipients, as well as newborn neonates. The objective of this study is to systematically review published literature on CMV in the MENA region to estimate its incidence in the region and describe its epidemiological and clinical significance. The literature was searched through four scientific databases: PubMed, Scopus, Science Direct, and Web of Science. A total of 72 studies from 11 countries satisfied the inclusion criteria, covering a period from 1988–2019. The CMV IgG seroprevalence ranged from 8.7%–99.2% (SD = 38.95%). CMV incidence in these countries ranged between 1.22% and 77% in transplant and transfusion recipients, with an increase in incidence with advanced age. However, the incidence rate was unclear for congenital CMV due to the variability of the reporting. This review highlights the need for more robust and well-designed studies to better estimate CMV incidence in the MENA region, standardize diagnostic criteria, and consider prophylactic and pre-emptive treatments to limit the morbidity and mortality of the disease.
Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration
Authors: Maharjan Pooja , Kim Daseul , Jin Minki , Ko Hwi Jin , Song Yeong Ho , Lee Yoonjin , Ahn Byul-Nim , Kim Si-Kyung , Lee Yujin , Shin Meong Cheol , Min Kyoung Ah , Yang JaeWook
Published: October 2019

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.
Customized Novel Design of 3D Printed Pregabalin Tablets for Intra-Gastric Floating and Controlled Release Using Fused Deposition Modeling
Authors: Lamichhane Shrawani , Park Jun-Bom , Sohn Dong Hwan , Lee Sangkil
Published: October 2019

Three-dimensional (3D) printing has been recently employed in the design and formulation of various dosage forms with the aim of on-demand manufacturing and personalized medicine. In this study, we formulated a floating sustained release system using fused deposition modeling (FDM). Filaments were prepared using hypromellose acetate succinate (HPMCAS), polyethylene glycol (PEG 400) and pregabalin as the active ingredient. Cylindrical tablets with infill percentages of 25%, 50% and 75% were designed and printed with the FDM printer. An optimized formulation (F6) was designed with a closed bottom layer and a partially opened top layer. Filaments and tablets were characterized by means of fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and thermogravimetric analysis (TGA). The results show that the processing condition did not have a significant effect on the stability of the drug and the crystallinity of the drug remained even after printing. A dissolution study revealed that drug release is faster in an open system with low infill percentage compared to closed systems and open systems with a high infill ratio. The optimized formulation (F6) with partially opened top layer showed zero-order drug release. The results show that FDM printing is suitable for the formulation of floating dosage form with the desired drug release profile.