bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression Programming (GEP) Modelling of Sustainable Building Materials including Mineral Admixtures for Novel Solutions
Authors: Kontoni Denise-Penelope N. , Onyelowe Kennedy C. , Ebid Ahmed M. , Jahangir Hashem , Rezazadeh Eidgahee Danial , Soleymani Atefeh , Ikpa Chidozie
Published: September 2022

In this study, the employment of the gene expression programming (GEP) technique in forecasting models on sustainable construction materials including mineral admixtures and civil engineering quantities (e.g., compressive strength), was investigated. Compared to the artificial neural networks (ANN) based formulations, which are often too complicated to be used, GEP-based derived models provide estimation equations that are reasonably simple and may be used for practical design purposes and even for hand calculations. Many popular models, such as best-fitted curves based on regression analyses, multi-linear regression (MLR), multinomial logistic regression (MNLR), and multinomial variate regression (MNVR), can also be used for construction materials properties modeling. However, due to the nonlinearity and complexity of the target properties, the models established using linear regression analyses may not reveal the precise behavior. Additionally, regression models lack generality, and this comes from the fact that some functions are defined for regression in classical regression techniques; while in the GEP approach, there is no predefined function to be considered, and it reproduces or omits various combinations of parameters to provide the formulation that fits the experimental outcomes. If the input parameters can be evaluated through simple laboratory or rapid measurements, and also a comprehensive experimental database is made available, the models can be constructed with optimal flexibility. Flexibility in choosing the complexity and fitness functions, such as RMSE, MAE, and MSE, might lead to better performance of the approach and well-capturing the governing pattern behind the material’s characteristics. There may be minor inaccuracies with this technique; however, the explicit mathematical expressions, which can be easily implemented in the design and analysis process, may cover the minor inaccuracies compared to ANN, support vector machine (SVM), and other intelligent approaches. Based on the presented study, sometimes it would be better to provide more than one GEP model and consider different combinations of input contributing variables to afford the possible initial feed for a more settled and comprehensive model. Mostly, GEP’s strengths as a superior machine learning technique in modeling the behavior of construction materials including mineral admixtures, leading to innovative solutions in civil engineering, have been presented.
Analysis of Protein-Protein Interactions for Intermolecular Bond Prediction
Authors: Tam Justin Z. , Palumbo Talulla , Miwa Julie M. , Chen Brian Y.
Published: September 2022

Protein-protein interactions often involve a complex system of intermolecular interactions between residues and atoms at the binding site. A comprehensive exploration of these interactions can help reveal key residues involved in protein-protein recognition that are not obvious using other protein analysis techniques. This paper presents and extends DiffBond, a novel method for identifying and classifying intermolecular bonds while applying standard definitions of bonds in chemical literature to explain protein interactions. DiffBond predicted intermolecular bonds from four protein complexes: Barnase-Barstar, Rap1a-raf, SMAD2-SMAD4, and a subset of complexes formed from three-finger toxins and nAChRs. Based on validation through manual literature search and through comparison of two protein complexes from the SKEMPI dataset, DiffBond was able to identify intermolecular ionic bonds and hydrogen bonds with high precision and recall, and identify salt bridges with high precision. DiffBond predictions on bond existence were also strongly correlated with observations of Gibbs free energy change and electrostatic complementarity in mutational experiments. DiffBond can be a powerful tool for predicting and characterizing influential residues in protein-protein interactions, and its predictions can support research in mutational experiments and drug design.
Content Determination and Release Characteristics of Six Components in the Different Phases of “Glycyrrhizaglabra-Nux vomica” Decoction by UPLC-MS/MS
Authors: Guo Yuyan , Shao Shuang , Zhang Wenjun , Li Chuncheng , Meng Zejun , Sun Shuang , Yang Dayu , Lü Shaowa
Published: September 2022

The decoction turns into a complex multiphase system following exposure to high temperature and a complex chemical environment. However, the differences in the concentration of key active ingredients in different phase states and the release of drugs in sedimentary phase have yet to be elucidated. A simple ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of brucine, strychnine, liquiritin, isoliquiritin, isoliquiritigenin and glycyrrhizic acid concentrations and it was applied to compare the content of different phases and measure the release characteristics of the sedimentary phase in “Glycyrrhiza glabra-Nux vomica” decoction (NGD). The results show that the method’s selectivity, precision (intraday and interday ≤ 2%), matrix effect (101–108%), recovery and stability results were acceptable according to the guidelines. The method is sensitive and reliable. The content determination results show that the most toxic strychnine in the sedimentary phase accounted for 75.70% of the total components. The different components exhibited differential release in different media, and its components were released in the artificial intestinal fluid up to 81.02% in 12 h. Several components conformed to the primary kinetic model and the Ritger–Peppas model, and the most toxic compound exhibited slow release, thus conforming to the Ritger–Peppas model. This study provides a standard of reference for studies investigating reduction in toxicity of the combination of Glycyrrhiza glabra (Glycyrrhiza glabra L.) and Nux vomica (Strychnos nux-vomica L.).
Polyphenolic Characterization, Antioxidant, Antihyaluronidase and Antimicrobial Activity of Young Leaves and Stem Extracts from Rubus caesius L.
Authors: Hering Anna , Stefanowicz-Hajduk Justyna , Hałasa Rafał , Olech Marta , Nowak Renata , Kosiński Piotr , Ochocka J. Renata
Published: September 2022

Fruits are the main food part of the European dewberry (Rubus caesius L.), known as a source of polyphenols and antioxidants, while very little attention is paid to leaves and stems, especially young first-year stems. The purpose of this work was to analyze for the first time water and ethanol extracts obtained from young, freshly developed, leaves and stems of the European dewberry to determine their antioxidant and biological activity, whereas most of the papers describe biological properties of leaves collected during summer or autumn. As the phytochemical profile changes during the growing season, the quantitative and qualitative content of flavonoid glycosides and flavonoid aglycones was analyzed using reversed phase liquid chromatography/electrospray ionization triple quadrupole mass spectrometry (LC-ESI-MS/MS) with multiple reaction monitoring (MRM). The ability to inhibit hyaluronidase as well as antioxidant activity (2,2 diphenyl-1-picrylhydrazyl: DPPH and ferric antioxidant power: FRAP) were estimated. Extracts were also analyzed against Gram-positive and Gram-negative bacteria. The results of the qualitative phytochemical analysis indicated the presence of flavonoid aglycones and flavonoid glycosides, with the highest amount of tiliroside, hyperoside, isoquercetin, astragalin, rutin and catechin in ethanol extracts. DPPH and FRAP tests proved the high antioxidant activity of the extracts from leaves or stems and the antihyaluronidase assay revealed for the first time that water and ethanol extracts obtained from the stems exhibited the ability to inhibit hyaluronidase activity resulting in an IC50 of 55.24 ± 3.21 and 68.7 ± 1.61 μg/mL, respectively. The antimicrobial activity has never been analyzed for European dewberry and was the highest for Clostridium bifermentans and Clostridium sporogenes—anaerobic sporulation rods as well as Enterococcus faecalis for both water and ethanol extracts.
Biowaste-Derived Carbon Dots: A Perspective on Biomedical Potentials
Authors: Rabiee Navid , Iravani Siavash , Varma Rajender S.
Published: September 2022

Today, sustainable and natural resources including biowastes have been considered attractive starting materials for the fabrication of biocompatible and biodegradable carbon dots (CDs) due to the benefits of availability, low cost, biorenewability, and environmentally benign attributes. These carbonaceous nanomaterials have been widely explored in the field of sensing/imaging, optoelectronics, photocatalysis, drug/gene delivery, tissue engineering, regenerative medicine, and cancer theranostics. Designing multifunctional biowaste-derived CDs with a high efficacy-to-toxicity ratio for sustained and targeted drug delivery, along with imaging potentials, opens a new window of opportunity toward theranostic applications. However, crucial challenges regarding the absorption/emission wavelength, up-conversion emission/multiphoton fluorescence mechanisms, and phosphorescence of these CDs still need to be addressed to attain the maximum functionality and efficacy. Future studies ought to focus on optimizing the synthesis techniques/conditions, evaluating the influence of nucleation/growth process on structures/properties, controlling their morphology/size, and finding the photoluminescence mechanisms. Reproducibility of synthesis techniques is another critically important factor that needs to be addressed in the future. Herein, the recent developments related to the biowaste-derived CDs with respect to their biomedical applications are deliberated, focusing on important challenges and future perspectives.
Ascorbate Is a Primary Antioxidant in Mammals
Authors: Fujii Junichi , Osaki Tsukasa , Bo Tomoki
Published: September 2022

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms.
Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides
Authors: Bailly Christian , Hénichart Jean-Pierre
Published: September 2022

The medicinal plant Artabotrys hexapetalus (synonyms: A.uncinatus and A. odoratissimus) is known as yingzhao in Chinese. Extracts of the plant have long been used in Asian folk medicine to treat various symptoms and diseases, including fevers, microbial infections, ulcers, hepatic disorders and other health problems. In particular, extracts from the roots and fruits of the plant are used for treating malaria. Numerous bioactive natural products have been isolated from the plant, mainly aporphine (artabonatines, artacinatine) and benzylisoquinoline (hexapetalines) alkaloids, terpenoids (artaboterpenoids), flavonoids (artabotrysides), butanolides (uncinine, artapetalins) and a small series of endoperoxides known as yingzhaosu A-to-D. These natural products confer antioxidant, anti-inflammatory and antiproliferative properties to the plant extracts. The lead compound yingzhaosu A displays marked activities against the malaria parasites Plasmodium falciparum and P. berghei. Total syntheses have been developed to access yingzhaosu compounds and analogues, such as the potent compound C14-epi-yingzhaosu A and simpler molecules with a dioxane unit. The mechanism of action of yingzhaosu A points to an iron(II)-induced degradation leading to the formation of two alkylating species, an unsaturated ketone and a cyclohexyl radical, which can then react with vital parasitic proteins. A bioreductive activation of yingzhaosu A endoperoxide can also occur with the heme iron complex. The mechanism of action of yingzhaosu endoperoxides is discussed, to promote further chemical and pharmacological studies of these neglected, but highly interesting bioactive compounds. Yingzhaosu A/C represent useful templates for designing novel antimalarial drugs.
Electrochemical and Spectroscopic Characterization of Oxidized Intermediate Forms of Vitamin E
Authors: Webster Richard D.
Published: September 2022

Vitamin E, a collection of lipophilic phenolic compounds based on chroman-6-ol, has a rich and fascinating oxidative chemistry involving a range of intermediate forms, some of which are proposed to be important in its biological functions. In this review, the available electrochemical and spectroscopic data on these oxidized intermediates are summarized, along with a discussion on how their lifetimes and chemical stability are either typical of similar phenolic and chroman-6-ol derived compounds, or atypical and unique to the specific oxidized isomeric form of vitamin E. The overall electrochemical oxidation mechanism for vitamin E can be summarized as involving the loss of two-electrons and one-proton, although the electron transfer and chemical steps can be controlled to progress along different pathways to prolong the lifetimes of discreet intermediates by modifying the experimental conditions (applied electrochemical potential, aqueous or non-aqueous solvent, and pH). Depending on the environment, the electrochemical reactions can involve single electron transfer (SET), proton-coupled electron transfer (PCET), as well as homogeneous disproportionation and comproportionation steps. The intermediate species produced via chemical or electrochemical oxidation include phenolates, phenol cation radicals, phenoxyl neutral radicals, dications, diamagnetic cations (phenoxeniums) and para–quinone methides. The cation radicals of all the tocopherols are atypically long-lived compared to the cation radicals of other phenols, due to their relatively weak acidity. The diamagnetic cation derived from α–tocopherol is exceptionally long-lived compared to the diamagnetic cations from the other β–, γ– and δ–isomers of vitamin E and compared with other phenoxenium cations derived from phenolic compounds. In contrast, the lifetime of the phenoxyl radical derived from α–tocopherol, which is considered to be critical in biological reactions, is typical for what is expected for a compound with its structural features. Over longer times via hydrolysis reactions, hydroxy para–quinone hemiketals and quinones can be formed from the oxidized intermediates, which can themselves undergo reduction processes to form intermediate anion radicals and dianions. Methods for generating the oxidized intermediates by chemical, photochemical and electrochemical methods are discussed, along with a summary of how the final products vary depending on the method used for oxidation. Since the intermediates mainly only survive in solution, they are most often monitored using UV-vis spectroscopy, FTIR or Raman spectroscopies, and EPR spectroscopy, with the spectroscopic techniques sometimes combined with fast photoinitiated excitation and time-resolved spectroscopy for detection of short-lived species.
Optimized Solid-Phase Mesh-Enhanced Sorption from Headspace (SPMESH) for Rapid Sub-ng/kg Measurements of 3-Isobutyl-2-methoxypyrazine (IBMP) in Grapes
Authors: Bates Terry L. , Rafson Jessica , Feng Hui , Pan Bruce S. , Mueller Benjamin R. J. , Yancey Benjamin , Fatigante William , Sacks Gavin L.
Published: September 2022

Parallel extraction of headspace volatiles from multiwell plates using sorbent sheets (HS-SPMESH) followed by direct analysis in real-time high-resolution mass spectrometry (DART-HRMS) can be used as a rapid alternative to solid-phase micro-extraction (SPME) gas-chromatography mass-spectrometry (GC-MS) for trace level volatile analyses. However, an earlier validation study of SPMESH-DART-MS using 3-isobutyl-2-methoxypyrazine (IBMP) in grape juice showed poor correlation between SPMESH-DART-MS and a gold standard SPME-GC-MS around the compound’s odor detection threshold (<10 ng/kg) in grape juice, and lacked sufficient sensitivity to detect IBMP at this concentration in grape homogenate. In this work, we report on the development and validation of an improved SPMESH extraction approach that lowers the limit of detection (LOD < 0.5 ng/kg), and regulates crosstalk between wells (<0.5%) over a calibration range of 0.5–100 ng/kg. The optimized SPMESH-DART-MS method was validated using Cabernet Sauvignon and Merlot grape samples harvested from commercial vineyards in the central valley of California (n = 302) and achieved good correlation and agreement with SPME-GC-MS (R2 = 0.84) over the native range of IBMP (<0.5–20 ng/kg). Coupling of SPMESH to a lower resolution triple quadrupole (QqQ)-MS via a new JumpShot-HTS DART source also achieved low ng/kg detection limits, and throughput was improved through positioning stage optimizations which reduced time spent on intra-well SPMESH areas.
Fast Detection of Cadmium in Chocolate by Solid Sampling Electrothermal Vaporization Atomic Absorption Spectrometry and Its Application on Dietary Exposure Risk Assessment
Authors: Jia Hongyu , Li Xue , Lan Guanyu , Wang Zhaohui , Feng Li , Mao Xuefei
Published: September 2022

In this work, a rapid detection method using solid sampling electrothermal vaporization atomic absorption spectrometry (SS-ETV-AAS) was established for cadmium in chocolate. The instrumental system includes a solid sampling ETV unit, a catalytic pyrolysis furnace, an AAS detector, and a gas supply system with only an air pump and a hydrogen generator. Herein, MgO material with 1.0–1.5 mm particle size was first employed to replace the kaolin filler previously used to further shorten the peak width and to thereby improve the sensitivity. With 350 mL/min of air, a chocolate sample was heated for 25 s from 435 to 464 °C to remove water and organic matrices; then, after supplying 240 mL/min hydrogen and turning down air to 120 mL/min, a N2/H2 mixture gas was formed to accelerate Cd vaporization from chocolate residue under 465 to 765 °C. Under the optimized conditions, the detection limit (LOD) was obviously lowered to 70 pg/g (vs. previous 150 pg/g) with R2 > 0.999; the relative standard deviations (RSD) of repeated measurements for real chocolate samples ranged from 1.5% to 6.4%, indicating a favorable precision; and the Cd recoveries were in the range of 93–107%, proving a satisfied accuracy. Thus, the total analysis time is less than 3 min without the sample digestion process. Thereafter, 78 chocolate samples with different brands from 9 producing countries in China market were collected and measured by this proposed method. Based on the measured Cd concentrations, a dietary exposure assessment was performed for Chinese residents, and the target hazard quotient (THQ) values are all less than 1, proving no significant health risk from intaking chocolate cadmium for Chinese residents.
Multicomponent Molecular Systems Based on Porphyrins, 1,3,5-Triazine and Carboranes: Synthesis and Characterization
Authors: Alpatova Victoria M. , Rys Evgeny G. , Kononova Elena G. , Khakina Ekaterina A. , Markova Alina A. , Shibaeva Anna V. , Kuzmin Vladimir A. , Ol’shevskaya Valentina A.
Published: September 2022

2,4,6-Trichloro-1,3,5-triazine (cyanuric chloride) is an excellent coupling reagent for the preparation of highly structured multifunctional molecules. Three component systems based on porphyrin, cyanuric chloride and carborane clusters were prepared by a one-pot stepwise amination of cyanuric chloride with 5-(4-aminophenyl)-10,15,20-triphenylporphyrin, followed by replacement of the remaining chlorine atoms with carborane S- or N-nucleophiles. Some variants of 1,3,5-triazine derivatives containing porphyrin, carborane and residues of biologically active compounds such as maleimide, glycine methyl ester as well as thioglycolic acid, mercaptoethanol and hexafluoroisopropanol were also prepared. A careful control of the reaction temperature during the substitution reactions will allow the synthesis of desired compounds in a good to high yields. The structures of synthesized compounds were determined with UV-vis, IR, 1H NMR, 11B NMR, MALDI-TOF or LC-MS spectroscopic data. The dark and photocytotoxicity as well as intracellular localization and photoinduced cell death for compounds 8, 9, 17, 18 and 24 were evaluated.
Effect of Nanoparticles of DOX and miR-125b on DNA Damage Repair in Glioma U251 Cells and Underlying Mechanisms
Authors: Wang Lin , Pan Tingting , Wang Yan , Yu Jiewen , Qu Peiyi , Chen Yue , Xin Hua , Wang Sicen , Liu Junxing , Wu Yan
Published: September 2022

Glioma is the most common primary craniocerebral malignant tumor, arising from the canceration of glial cells in the brain and spinal cord. The quality of life and prognosis of patients with this disease are still poor. Doxorubicin (DOX) is one of the most traditional and economical chemotherapeutic drugs for the treatment of glioma, but its toxic effect on normal cells and the resistance of tumor cells to DOX make the application of DOX in the treatment of glioma gradually less effective. To solve this problem, we co-encapsulated DOX and endogenous tumor suppressor miR-125b into nanoparticles (NPs) by nanoprecipitation methods, and passively targeted them into glioma cells. In vitro experiments show that miR-125b and DOX can be effectively encapsulated into nanoparticles with different ratios, and by targeting YES proto-oncogene 1 (YES1), they can affect the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/p53 pathway and induce brain glioma cell apoptosis. They can also affect the DNA damage repair process and inhibit cell proliferation. The obtained data suggest that co-delivery of DOX and miR-125b could achieve synergistic effects on tumor suppression. Nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.
Immobilization of Ionic Liquid on a Covalent Organic Framework for Effectively Catalyzing Cycloaddition of CO2 to Epoxides
Authors: Yan Qianqian , Liang Hao , Wang Shenglin , Hu Hui , Su Xiaofang , Xiao Songtao , Xu Huanjun , Jing Xuechao , Lu Fei , Gao Yanan
Published: September 2022

Transforming CO2 into value-added chemicals has been an important subject in recent years. The development of a novel heterogeneous catalyst for highly effective CO2 conversion still remains a great challenge. As an emerging class of porous organic polymers, covalent organic frameworks (COFs) have exhibited superior potential as catalysts for various chemical reactions, due to their unique structure and properties. In this study, a layered two-dimensional (2D) COF, IM4F-Py-COF, was prepared through a three-component condensation reaction. Benzimidazole moiety, as an ionic liquid precursor, was integrated onto the skeleton of the COF using a benzimidazole-containing building unit. Ionization of the benzimidazole framework was then achieved through quaternization with 1-bromobutane to produce an ionic liquid-immobilized COF, i.e., BMIM4F-Py-COF. The resulting ionic COF shows excellent catalytic activity in promoting the chemical fixation of CO2 via reaction with epoxides under solvent-free and co-catalyst-free conditions. High porosity, the one-dimensional (1D) open-channel structure of the COF and the high catalytic activity of ionic liquid may contribute to the excellent catalytic performance. Moreover, the COF catalyst could be reused at least five times without significant loss of its catalytic activity.
A Novel Family of Cage-like (CuLi, CuNa, CuK)-phenylsilsesquioxane Complexes with 8-Hydroxyquinoline Ligands: Synthesis, Structure, and Catalytic Activity
Authors: Bilyachenko Alexey N. , Khrustalev Victor N. , Zueva Anna Y. , Titova Ekaterina M. , Astakhov Grigorii S. , Zubavichus Yan V. , Dorovatovskii Pavel V. , Korlyukov Alexander A. , Shul’pina Lidia S. , Shubina Elena S. , Kozlov Yuriy N. , Ikonnikov Nikolay S. , Gelman Dmitri , Shul’pin Georgiy B.
Published: September 2022

The first examples of metallasilsesquioxane complexes, including ligands of the 8-hydroxyquinoline family 1–9, were synthesized, and their structures were established by single crystal X-ray diffraction using synchrotron radiation. Compounds 1–9 tend to form a type of sandwich-like cage of Cu4M2 nuclearity (M = Li, Na, K). Each complex includes two cisoid pentameric silsesquioxane ligands and two 8-hydroxyquinoline ligands. The latter coordinates the copper ions and corresponding alkaline metal ions (via the deprotonated oxygen site). A characteristic (size) of the alkaline metal ion and a variation of characteristics of nitrogen ligands (8-hydroxyquinoline vs. 5-chloro-8-hydroxyquinoline vs. 5,7-dibromo-8-hydroxyquinoline vs. 5,7-diiodo-8-hydroxyquinoline) are highly influential for the formation of the supramolecular structure of the complexes 3a, 5, and 7–9. The Cu6Na2-based compound 2 exhibits high catalytic activity towards the oxidation of (i) hydrocarbons by H2O2 activated with HNO3, and (ii) alcohols by tert-butyl hydroperoxide. Studies of kinetics and their selectivity has led us to conclude that it is the hydroxyl radicals that play a crucial role in this process.
Hybrids of 1,4-Quinone with Quinoline Derivatives: Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1)
Authors: Kadela-Tomanek Monika , Jastrzębska Maria , Chrobak Elwira , Bębenek Ewa , Latocha Małgorzata
Published: September 2022

Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods. The enzymatic assay used showed that these compounds were a suitable DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. Hybrids were tested in vitro against a panel of human cell lines including melanoma, breast, and lung cancers. They showed also a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activity of the studied hybrids was increasing against the cell lines with higher NQO1 protein level, such as breast (MCF-7 and T47D) and lung (A549) cancers. Selected hybrids were tested for the transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and the apoptosis pathway (BCL-2 and BAX). The molecular docking was used to examine the probable interaction between the hybrids and NQO1 protein.
Herbal Arsenal against Skin Ailments: A Review Supported by In Silico Molecular Docking Studies
Authors: Singab Abdel Nasser B. , Mostafa Nada M. , Fawzy Iten M. , Bhatia Deepika , Suryawanshi Pooja Tanaji , Kabra Atul
Published: September 2022

Maintaining healthy skin is important for a healthy body. At present, skin diseases are numerous, representing a major health problem affecting all ages from neonates to the elderly worldwide. Many people may develop diseases that affect the skin, including cancer, herpes, and cellulitis. Long-term conventional treatment creates complicated disorders in vital organs of the body. It also imposes socioeconomic burdens on patients. Natural treatment is cheap and claimed to be safe. The use of plants is as old as mankind. Many medicinal plants and their parts are frequently used to treat these diseases, and they are also suitable raw materials for the production of new synthetic agents. A review of some plant families, viz., Fabaceae, Asteraceae, Lamiaceae, etc., used in the treatment of skin diseases is provided with their most common compounds and in silico studies that summarize the recent data that have been collected in this area.
Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
Authors: Kang Songyao , Chen Tingting , Hao Zhihui , Yang Xiao , Wang Mingfa , Zhang Zhifang , Hao Sijia , Lang Fengting , Hao Hongxia
Published: September 2022

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats’ kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.
Design of Deep Eutectic Systems: Plastic Crystalline Materials as Constituents
Authors: Alhadid Ahmad , Nasrallah Sahar , Mokrushina Liudmila , Minceva Mirjana
Published: September 2022

Deep eutectic solvents (DESs) are a class of green and tunable solvents that can be formed by mixing constituents having very low melting entropies and enthalpies. As types of materials that meet these requirements, plastic crystalline materials (PCs) with highly symmetrical and disordered crystal structures can be envisaged as promising DES constituents. In this work, three PCs, namely, neopentyl alcohol, pivalic acid, and neopentyl glycol, were studied as DES constituents. The solid–plastic transitions and melting properties of the pure PCs were studied using differential scanning calorimetry. The solid–liquid equilibrium phase diagrams of four eutectic systems containing the three PCs, i.e., L-menthol/neopentyl alcohol, L-menthol/pivalic acid, L-menthol/neopentyl glycol, and choline chloride/neopentyl glycol, were measured. Despite showing near-ideal behavior, the four studied eutectic systems exhibited depressions at the eutectic points, relative to the melting temperatures of the pure constituents, that were similar to or even larger than those of strongly nonideal eutectic systems. These findings highlight that a DES can be formed when PCs are used as constituents, even if the eutectic system is ideal.
Discovery of Novel PI3Kδ Inhibitors Based on the p110δ Crystal Structure
Authors: Jia Wenqing , Luo Shuyu , Zhao Wennan , Xu Weiren , Zhong Yuxu , Kong Dexin
Published: September 2022

PI3Kδ is a key mediator of B-cell receptor signaling and plays an important role in the pathogenesis of certain hematological malignancies, such as chronic lymphocytic leukemia. Idelalisib, which targets PI3Kδ specifically, is the first approved PI3K inhibitor for cancer therapy. Recently, we carried out virtual screening, cell-based assays, adapta kinase assays, and molecular dynamic analysis to discover novel PI3Kδ inhibitors and identified NSC348884 as a lead PI3Kδ inhibitor. NSC348884 had an excellent docking score, potent PI3Kδ-inhibitory activity, antitumor effects on various cancer cell lines, and a favorable binding mode with the active site of PI3Kδ. Moreover, through the structural modification of NSC348884, we further discovered comp#1, which forms H-bonds with both Val828 and Lys779 in the ATP binding pocket of PI3Kδ, with a more favorable conformation binding to PI3Kδ. In addition, we found that N1, N1, N2-trimethyl-N2-((6-methyl-1H-benzo[d]imidazol-2-yl) methyl) ethane-1,2-diamine might be a potential scaffold structure. Thus, the result of this study provides a far more efficient approach for discovering novel inhibitors targeting PI3Kδ.
Drug-Inclusive Inorganic–Organic Hybrid Systems for the Controlled Release of the Osteoporosis Drug Zoledronate
Authors: Vassaki Maria , Lazarou Savvina , Turhanen Petri , Choquesillo-Lazarte Duane , Demadis Konstantinos
Published: September 2022

Bisphosphonates (BPs) are common pharmaceutical treatments used for calcium- and bone-related disorders, the principal one being osteoporosis. Their antiresorptive action is related to their high affinity for hydroxyapatite, the main inorganic substituent of bone. On the other hand, the phosphonate groups on their backbone make them excellent ligands for metal ions. The combination of these properties finds potential application in the utilization of such systems as controlled drug release systems (CRSs). In this work, the third generation BP drug zoledronate (ZOL) was combined with alkaline earth metal ions (e.g., Sr2+ and Ba2+) in an effort to synthesize new materials. These metal–ZOL compounds can operate as CRSs when exposed to appropriate experimental conditions, such as the low pH of the human stomach, thus releasing the active drug ZOL. CRS networks containing Sr2+ or Ba2 and ZOL were physicochemically and structurally characterized and were evaluated for their ability to release the free ZOL drug during an acid-driven hydrolysis process. Various release and kinetic parameters were determined, such as initial rates and release plateau values. Based on the drug release results of this study, there was an attempt to correlate the ZOL release efficiency with the structural features of these CRSs.
A Selective Review and Virtual Screening Analysis of Natural Product Inhibitors of the NLRP3 Inflammasome
Authors: El-Sayed Sherihan , Freeman Sally , Bryce Richard A.
Published: September 2022

The NLRP3 inflammasome is currently an exciting target for drug discovery due to its role in various inflammatory diseases; however, to date, no NLRP3 inhibitors have reached the clinic. Several studies have used natural products as hit compounds to facilitate the design of novel selective NLRP3 inhibitors. Here, we review selected natural products reported in the literature as NLRP3 inhibitors, with a particular focus on those targeting gout. To complement this survey, we also report a virtual screen of the ZINC20 natural product database, predicting favored chemical features that can aid in the design of novel small molecule NLRP3 inhibitors.
The First 5′-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation
Authors: Tatarinov Dmitry A. , Garifullin Bulat F. , Belenok Mayya G. , Andreeva Olga V. , Strobykina Irina Yu , Shepelina Anna V. , Zarubaev Vladimir V. , Slita Alexander V. , Volobueva Alexandrina S. , Saifina Liliya F. , Shulaeva Marina M. , Semenov Vyacheslav E. , Kataev Vladimir E.
Published: September 2022

A series of 5′-phosphorylated (dialkyl phosphates, diaryl phosphates, phosphoramidates, H-phosphonates, phosphates) 1,2,3-triazolyl nucleoside analogues in which the 1,2,3-triazole-4-yl-β-D-ribofuranose fragment is attached via a methylene group or a butylene chain to the N-1 atom of the heterocycle moiety (uracil or quinazoline-2,4-dione) was synthesized. All compounds were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1). Antiviral assays revealed three compounds, 13b, 14b, and 17a, which showed moderate activity against influenza virus A (H1N1) with IC50 values of 17.9 μM, 51 μM, and 25 μM, respectively. In the first two compounds, the quinazoline-2,4-dione moiety is attached via a methylene or a butylene linker, respectively, to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-diphenyl phosphate substituent. In compound 17a, the uracil moiety is attached via the methylene unit to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-(phenyl methoxy-L-alaninyl)phosphate substituent. The remaining compounds appeared to be inactive against influenza virus A/PR/8/34/(H1N1). The results of molecular docking simulations indirectly confirmed the literature data that the inhibition of viral replication is carried out not by nucleoside analogues themselves, but by their 5′-triphosphate derivatives.
Essential Oils as a Source of Ecofriendly Insecticides for Drosophila suzukii (Diptera: Drosophilidae) and Their Potential Non-Target Effects
Authors: Souza Michele Trombin de , Souza Mireli Trombin de , Morais Maíra Chagas , Oliveira Daiana da Costa , Melo Douglas José de , Figueiredo Leonardo , Zarbin Paulo Henrique Gorgatti , Zawadneak Maria Aparecida Cassilha , Bernardi Daniel
Published: September 2022

The spotted wing drosophila (Drosophila suzukii) is one of the main invasive pests of small fruits in the world. Thus, 19 essential oils (EOs) were selected to analyze the effects through toxicity and repellency on oviposition and D. suzukii adults. In addition, their lethal and sublethal effects on the pupal endoparasitoid Trichopria anastrephae were evaluated. The EOs of C. flexuosus and Mentha spp. had the highest toxicity observed in the topical application bioassay for D. suzukii. In contrast, the EOs of C. verum, C. citratus QT citratus, and C. winterianus showed the highest toxicity in the ingestion bioassay for D. suzukii. The dry residues of C. verum and C. citratus QT citratus reduced the oviposition of D. suzukii. In the repellency bioassays, the 19 EOs analyzed repelled ≅ 90% of the D. suzukii females. All EOs evaluated using the LC90 values of the products provided mortality of less than 20% of T. anastrephae adults and did not cause a reduction in the parasitism of surviving T. anastrephae females. We conclude that the EOs evaluated have the potential to be used in the management of D. suzukii. They can also serve as selective active ingredients for the formulation and synthesis of new biopesticides.
Antiprotozoal Activity of Azabicyclo-Nonanes Linked to Tetrazole or Sulfonamide Cores
Authors: Dolensky Johanna , Hinteregger Clemens , Leitner Andreas , Seebacher Werner , Saf Robert , Belaj Ferdinand , Mäser Pascal , Kaiser Marcel , Weis Robert
Published: September 2022

N-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity. A series with terminal tetrazole or sulfonamido partial structure was prepared. The structures of all new compounds were confirmed by NMR and IR spectroscopy and by mass spectral data. A single crystal structure analysis enabled the distinction between isomers. The antiprotozoal activities were examined in vitro against strains of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The most active sulfonamide and tetrazole derivates showed activities in the submicromolar range.
Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents
Authors: Ivasechko Iryna , Yushyn Ihor , Roszczenko Piotr , Senkiv Julia , Finiuk Nataliya , Lesyk Danylo , Holota Serhii , Czarnomysy Robert , Klyuchivska Olga , Khyluk Dmytro , Kashchak Nataliya , Gzella Andrzej , Bielawski Krzysztof , Bielawska Anna , Stoika Rostyslav , Lesyk Roman
Published: September 2022

Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.
Effects of Chemical Structures Interacting with Amine Oxidases on Glucose, Lipid and Hydrogen Peroxide Handling by Human Adipocytes
Authors: Carpéné Christian , Viana Pénélope , Iffiú-Soltesz Zsuzsa , Tapolcsányi Pál , Földi Anna Ágota , Mátyus Péter , Dunkel Petra
Published: September 2022

Benzylamine is a natural molecule present in food and edible plants, capable of activating hexose uptake and inhibiting lipolysis in human fat cells. These effects are dependent on its oxidation by amine oxidases present in adipocytes, and on the subsequent hydrogen peroxide production, known to exhibit insulin-like actions. Virtually, other substrates interacting with such hydrogen peroxide-releasing enzymes potentially can modulate lipid accumulation in adipose tissue. Inhibition of such enzymes has also been reported to influence lipid deposition. We have therefore studied in human adipocytes the lipolytic and lipogenic activities of pharmacological entities designed to interact with amine oxidases highly expressed in this cell type: the semicarbazide-sensitive amine oxidase (SSAO also known as PrAO or VAP-1) and the monoamine oxidases (MAO). The results showed that SZV-2016 and SZV-2017 behaved as better substrates than benzylamine, releasing hydrogen peroxide once oxidized, and reproduced or even exceeded its insulin-like metabolic effects in fat cells. Additionally, several novel SSAO inhibitors, such as SZV-2007 and SZV-1398, have been evidenced and shown to inhibit benzylamine metabolic actions. Taken as a whole, our findings reinforce the list of molecules that influence the regulation of triacylglycerol assembly/breakdown, at least in vitro in human adipocytes. The novel compounds deserve deeper investigation of their mechanisms of interaction with SSAO or MAO, and constitute potential candidates for therapeutic use in obesity and diabetes.
Ionization of Decamethylmanganocene: Insights from the DFT-Assisted Laser Spectroscopy
Authors: Ketkov Sergey , Tzeng Sheng-Yuan , Rychagova Elena , Tzeng Wen-Bih
Published: September 2022

Metallocenes represent one of the most important classes of organometallics with wide prospects for practical use in various fields of chemistry, materials science, molecular electronics, and biomedicine. Many applications of these metal complexes are based on their ability to form molecular ions. We report the first results concerning the changes in the molecular and electronic structure of decamethylmanganocene, Cp*2Mn, upon ionization provided by the high-resolution mass-analyzed threshold ionization (MATI) spectroscopy supported by DFT calculations. The precise ionization energy of Cp*2Mn is determined as 5.349 ± 0.001 eV. The DFT modeling of the MATI spectrum shows that the main structural deformations accompanying the detachment of an electron consist in the elongation of the Mn-C bonds and a change in the Me out-of-plane bending angles. Surprisingly, the DFT calculations predict that most of the reduction in electron density (ED) upon ionization is associated with the hydrogen atoms of the substituents, despite the metal character of the ionized orbital. However, the ED difference isosurfaces reveal a complex mechanism of the charge redistribution involving also the carbon atoms of the molecule.
Isolation of Mirificin and Other Bioactive Isoflavone Glycosides from the Kudzu Root Lyophilisate Using Centrifugal Partition and Flash Chromatographic Techniques
Authors: Maciejewska-Turska Magdalena , Pecio Łukasz , Zgórka Grażyna
Published: September 2022

Pueraria lobata (Willd.) Ohwi is a legume taxon native to Southeast Asia and widely used in traditional medicine systems of that region. The therapeutic applications of the underground parts of this species (known as kudzu root) are related to its high content of isoflavones, mainly the characteristic C-glycoside derivatives. Within this group, the most explored compound both phytochemically and pharmacologically is puerarin. However, current scientific findings document important anti-biodegenerative effects for some of the minor isoflavones from kudzu roots. Therefore, the main objective of the study was to develop an original preparative method that allowed the efficient isolation of closely related hydrophilic daidzein C-glycosides, including mirificin, from vacuum-dried aqueous-ethanolic extracts of kudzu roots. For this purpose, the combined centrifugal partition (CPC) and flash chromatographic (FC) techniques were elaborated and used. The optimized biphasic solvent system in CPC, with ethyl acetate, ethanol, water, and 0.5% (V/V) acetic acid as a mobile phase modifier, enabled the purification and separation of the polar fraction containing bioactive isoflavones and ultimately the isolation of mirificin, 3′-hydroxy- and 3′-methoxypuerarin, puerarin, and daidzin using FC. The identity of isoflavones was confirmed using spectroscopic (UV absorption and nuclear magnetic resonance) and mass spectrometric methods. The determined purity of isolated mirificin was 63%.