Molecules

18 pages, 3985 KiB

Open AccessArticle

2-Deoxy-d-glucose Promotes Buforin IIb-Induced Cytotoxicity in Prostate Cancer DU145 Cells and Xenograft Tumors

by Yangke Wanyan, Xixi Xu, Kehang Liu, Huidan Zhang, Junai Zhen, Rong Zhang, Jumei Wen, Ping Liu and Yuqing Chen

Molecules 2020, 25(23), 5778; https://doi.org/10.3390/molecules25235778 - 7 Dec 2020

Cited by 8 | Viewed by 3590

Abstract

Inhibition of the glycolytic pathway is a critical strategy in anticancer therapy because of the role of aerobic glycolysis in cancer cells. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) has shown potential in combination with other anticancer agents. Buforin IIb is an effective [...] Read more.

Inhibition of the glycolytic pathway is a critical strategy in anticancer therapy because of the role of aerobic glycolysis in cancer cells. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) has shown potential in combination with other anticancer agents. Buforin IIb is an effective antimicrobial peptide (AMP) with broad-spectrum anticancer activity and selectivity. The efficacy of combination treatment with 2-DG and buforin IIb in prostate cancer remains unknown. Here, we tested the efficacy of buforin IIb as a mitochondria-targeting AMP in the androgen-independent human prostate cancer cell line DU145. Combining 2-DG with buforin IIb had a synergistic toxic effect on DU145 cells and mouse xenograft tumors. Combination treatment with 2-DG and buforin IIb caused stronger proliferation inhibition, greater G1 cell cycle arrest, and higher apoptosis than either treatment alone. Combination treatment dramatically decreased L-lactate production and intracellular ATP levels, indicating severe inhibition of glycolysis and ATP production. Flow cytometry and confocal laser scanning microscopy results indicate that 2-DG may increase buforin IIb uptake by DU145 cells, thereby increasing the mitochondria-targeting capacity of buforin IIb. This may partly explain the effect of combination treatment on enhancing buforin IIb-induced apoptosis. Consistently, 2-DG increased mitochondrial dysfunction and upregulated Bax/Bcl-2, promoting cytochrome c release to initiate procaspase 3 cleavage induced by buforin IIb. These results suggest that 2-DG sensitizes prostate cancer DU145 cells to buforin IIb. Moreover, combination treatment caused minimal hemolysis and cytotoxicity to normal WPMY-1 cells. Collectively, the current study demonstrates that dual targeting of glycolysis and mitochondria by 2-DG and buforin IIb may be an effective anticancer strategy for the treatment of some advanced prostate cancer. Full article

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14 pages, 1181 KiB

Open AccessReview

The Ketamine Antidepressant Story: New Insights

by Tahani K. Alshammari

Molecules 2020, 25(23), 5777; https://doi.org/10.3390/molecules25235777 - 7 Dec 2020

Cited by 15 | Viewed by 12930

Abstract

Ketamine is a versatile agent primarily utilized as a dissociative anesthetic, which acts by blocking the excitatory receptor N-methyl-d-aspartate receptor (NMDA). It functions to inhibit the current of both Na⁺ and K⁺ voltage-gated channels, thus preventing serotonin and [...] Read more.

Ketamine is a versatile agent primarily utilized as a dissociative anesthetic, which acts by blocking the excitatory receptor N-methyl-d-aspartate receptor (NMDA). It functions to inhibit the current of both Na⁺ and K⁺ voltage-gated channels, thus preventing serotonin and dopamine reuptake. Studies have indicated that administering a single subanesthetic dose of ketamine relieves depression rapidly and that the effect is sustained. For decades antidepressant agents were based on the monoamine theory. Although ketamine may not be the golden antidepressant, it has opened new avenues toward mechanisms involved in the pathology of treatment-resistant depression and achieving rapid antidepressant effects. Thus, preclinical studies focusing on deciphering the molecular mechanisms involved in the antidepressant action of ketamine will assist in the development of a new antidepressant. This review was conducted to elucidate the emerging pathways that can explain the complex dose-dependent mechanisms achieved by administering ketamine to treat major depressive disorders. Special attention was paid to reviewing the literature on hydroxynorketamines, which are ketamine metabolites that have recently attracted attention in the context of depression. Full article

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43 pages, 2119 KiB

Open AccessReview

Antitumor Drugs and Their Targets

by Zlatko Dembic

Molecules 2020, 25(23), 5776; https://doi.org/10.3390/molecules25235776 - 7 Dec 2020

Cited by 57 | Viewed by 11011

Abstract

Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer [...] Read more.

Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies. Full article

(This article belongs to the Special Issue Translational Approach to Antitumor Drugs)

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14 pages, 1801 KiB

Open AccessArticle

Expression of Somatostatin Receptor Subtypes (SSTR-1–SSTR-5) in Pediatric Hematological and Oncological Disorders

by Kristof Harda, Zsuzsanna Szabo, Eva Juhasz, Balazs Dezso, Csongor Kiss, Andrew V. Schally and Gabor Halmos

Molecules 2020, 25(23), 5775; https://doi.org/10.3390/molecules25235775 - 7 Dec 2020

Cited by 7 | Viewed by 5348

Abstract

Hematological and oncological disorders represent leading causes of childhood mortality. Neuropeptide somatostatin (SST) has been previously demonstrated in various pediatric tumors, but limited information exists on the expression and characteristics of SST receptors (SSTR) in hematological and oncological disorders of children. We aimed [...] Read more.

Hematological and oncological disorders represent leading causes of childhood mortality. Neuropeptide somatostatin (SST) has been previously demonstrated in various pediatric tumors, but limited information exists on the expression and characteristics of SST receptors (SSTR) in hematological and oncological disorders of children. We aimed to investigate the expression of mRNA for SSTR subtypes (SSTR-1–5) in 15 pediatric hematological/oncological specimens by RT-PCR. The presence and binding characteristics of SSTRs were further studies by ligand competition assay. Our results show that the pediatric tumor samples highly expressed mRNA for the five SSTR subtypes with various patterns. The mRNA for SSTR-2 was detected in all specimens independently of their histological type. A Hodgkin lymphoma sample co-expressed mRNA for all five SSTR subtypes. SSTR-3 and SSTR-5 were detected only in malignant specimens, such as rhabdomyosarcoma, Hodgkin lymphoma, acute lymphoblastic leukemia, and a single nonmalignant condition, hereditary spherocytosis. The incidence of SSTR-1 and SSTR-4 was similar (60%) in the 15 specimens investigated. Radioligand binding studies demonstrated the presence of specific SSTRs and high affinity binding of SST analogs in pediatric solid tumors investigated. The high incidence of SSTRs in hematological and oncological disorders in children supports the merit of further investigation of SSTRs as molecular targets for diagnosis and therapy. Full article

(This article belongs to the Collection Novel Approache of Anticancer Therapy)

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14 pages, 2027 KiB

Open AccessArticle

Simultaneous Ultrasound and Heat Enhance Functional Properties of Glycosylated Lactoferrin

by Zhipeng Li, Dexue Ma, Yiyang He, Siqi Guo, Fuguo Liu and Xuebo Liu

Molecules 2020, 25(23), 5774; https://doi.org/10.3390/molecules25235774 - 7 Dec 2020

Cited by 15 | Viewed by 3100

Abstract

Protein-polysaccharide covalent complexes exhibit better physicochemical and functional properties than single protein or polysaccharide. To promote the formation of the covalent complex from lactoferrin (LF) and beet pectin (BP), we enhanced the Maillard reaction between LF and BP by using an ultrasound-assisted treatment [...] Read more.

Protein-polysaccharide covalent complexes exhibit better physicochemical and functional properties than single protein or polysaccharide. To promote the formation of the covalent complex from lactoferrin (LF) and beet pectin (BP), we enhanced the Maillard reaction between LF and BP by using an ultrasound-assisted treatment and studied the structure and functional properties of the resulting product. The reaction conditions were optimized by an orthogonal experimental design, and the highest grafting degree of 55.36% was obtained by ultrasonic treatment at 300 W for 20 min and at LF concentration of 20 g/L and BP concentration of 9 g/L. The formation of LF-BP conjugates was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared (FTIR) spectroscopy. Ultrasound-assisted treatment can increase the surface hydrophobicity, browning index, 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) free radicals scavenging activity of LF due to the changes in the spatial configuration and formation of Maillard reaction products. The thermal stability, antioxidant activity and emulsifying property of LF were significantly improved after combining with BP. These findings reveal the potential application of modified proteins by ultrasonic and heat treatment. Full article

(This article belongs to the Special Issue Food Biopolymers and Colloids: A Theme Issue in Honor of Professor David Julian McClements)

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26 pages, 12602 KiB

Open AccessArticle

Pharmacophore Modeling and 3D-QSAR Study of Indole and Isatin Derivatives as Antiamyloidogenic Agents Targeting Alzheimer’s Disease

by Rosa Purgatorio, Nicola Gambacorta, Marco Catto, Modesto de Candia, Leonardo Pisani, Alba Espargaró, Raimon Sabaté, Saverio Cellamare, Orazio Nicolotti and Cosimo D. Altomare

Molecules 2020, 25(23), 5773; https://doi.org/10.3390/molecules25235773 - 7 Dec 2020

Cited by 17 | Viewed by 5008

Abstract

Thirty-six novel indole-containing compounds, mainly 3-(2-phenylhydrazono) isatins and structurally related 1H-indole-3-carbaldehyde derivatives, were synthesized and assayed as inhibitors of beta amyloid (Aβ) aggregation, a hallmark of pathophysiology of Alzheimer’s disease. The newly synthesized molecules spanned their IC₅₀ values from sub- [...] Read more.

Thirty-six novel indole-containing compounds, mainly 3-(2-phenylhydrazono) isatins and structurally related 1H-indole-3-carbaldehyde derivatives, were synthesized and assayed as inhibitors of beta amyloid (Aβ) aggregation, a hallmark of pathophysiology of Alzheimer’s disease. The newly synthesized molecules spanned their IC₅₀ values from sub- to two-digit micromolar range, bearing further information into structure-activity relationships. Some of the new compounds showed interesting multitarget activity, by inhibiting monoamine oxidases A and B. A cell-based assay in tau overexpressing bacterial cells disclosed a promising additional activity of some derivatives against tau aggregation. The accumulated data of either about ninety published and thirty-six newly synthesized molecules were used to generate a pharmacophore hypothesis of antiamyloidogenic activity exerted in a wide range of potencies, satisfactorily discriminating the ‘active’ compounds from the ‘inactive’ (poorly active) ones. An atom-based 3D-QSAR model was also derived for about 80% of ‘active’ compounds, i.e., those achieving finite IC₅₀ values lower than 100 μM. The 3D-QSAR model (encompassing 4 PLS factors), featuring acceptable predictive statistics either in the training set (n = 45, q² = 0.596) and in the external test set (n = 14, r²_ext = 0.695), usefully complemented the pharmacophore model by identifying the physicochemical features mainly correlated with the Aβ anti-aggregating potency of the indole and isatin derivatives studied herein. Full article

(This article belongs to the Special Issue Indole and Its Bioisosteric Replacements in Medicinal Chemistry)

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19 pages, 881 KiB

Open AccessReview

Mechanistic Aspects and Therapeutic Potential of Quercetin against COVID-19-Associated Acute Kidney Injury

by Lúcio Ricardo Leite Diniz, Marilia Trindade de Santana Souza, Allana Brunna Sucupira Duarte and Damião Pergentino de Sousa

Molecules 2020, 25(23), 5772; https://doi.org/10.3390/molecules25235772 - 7 Dec 2020

Cited by 40 | Viewed by 8126

Abstract

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. [...] Read more.

The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients. Full article

(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential 2021)

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13 pages, 1793 KiB

Open AccessArticle

Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro

by Fanni Földes, Mónika Madai, Henrietta Papp, Gábor Kemenesi, Brigitta Zana, Lili Geiger, Katalin Gombos, Balázs Somogyi, Ildikó Bock-Marquette and Ferenc Jakab

Molecules 2020, 25(23), 5771; https://doi.org/10.3390/molecules25235771 - 7 Dec 2020

Cited by 5 | Viewed by 3021

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV [...] Read more.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments. Full article

(This article belongs to the Special Issue Antiviral Agents for RNA-Virus Infection)

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17 pages, 3686 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Halogenated E-Stilbenols as Promising Antiaging Agents

by Ester Sara Di Filippo, Letizia Giampietro, Barbara De Filippis, Marwa Balaha, Vincenzo Ferrone, Marcello Locatelli, Tiziana Pietrangelo, Angela Tartaglia, Rosa Amoroso and Stefania Fulle

Molecules 2020, 25(23), 5770; https://doi.org/10.3390/molecules25235770 - 7 Dec 2020

Cited by 12 | Viewed by 3274

Abstract

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations [...] Read more.

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations of reactive oxygen species. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RSV) plays a critical role in slowing the aging process but has a poor bioavailabity after oral intake. In this present work, a series of RSV derivatives was designed, synthesized, and evaluated as potential antioxidant agents. These derivatives contain substituents with different electronic and steric properties in different positions of aromatic rings. This kind of substituents affects the activity and the bioavailability of these compounds compared with RSV used as reference compound. Studies of Log P values demonstrated that the introduction of halogens gives the optimum lipophilicity to be considered promising active agents. Among them, compound 6 showed the higher antioxidant activity than RSV. The presence of trifluoromethyl group together with a chlorine atom increased the antioxidant activity compared to RSV. Full article

(This article belongs to the Special Issue Synthesis and Identification of Small Compounds Active in Neurodegeneration)

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7 pages, 221 KiB

Open AccessEditorial

Biological Activities of Natural Products

by Halina Maria Ekiert and Agnieszka Szopa

Molecules 2020, 25(23), 5769; https://doi.org/10.3390/molecules25235769 - 7 Dec 2020

Cited by 92 | Viewed by 6805

Abstract

Natural products and their biological activities are currently a subject of great interest in the pharmaceutical, health food, and cosmetics industries, and numbers of scientific studies in this field are increasing rapidly [...] Full article

(This article belongs to the Special Issue Biological Activities of Natural Products)

15 pages, 2103 KiB

Open AccessReview

Ferula L. Plant Extracts and Dose-Dependent Activity of Natural Sesquiterpene Ferutinin: From Antioxidant Potential to Cytotoxic Effects

by Roberta Macrì, Vincenzo Musolino, Micaela Gliozzi, Cristina Carresi, Jessica Maiuolo, Saverio Nucera, Miriam Scicchitano, Francesca Bosco, Federica Scarano, Stefano Ruga, Maria Caterina Zito, Lorenza Guarnieri, Ezio Bombardelli and Vincenzo Mollace

Molecules 2020, 25(23), 5768; https://doi.org/10.3390/molecules25235768 - 7 Dec 2020

Cited by 30 | Viewed by 5301

Abstract

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is [...] Read more.

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug. Full article

(This article belongs to the Special Issue Natural Antioxidants: Chemistry, Health Beneficial Properties, and Potential Application)

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12 pages, 1050 KiB

Open AccessCommunication

The Callus of Phaseolus coccineus and Glycine max Biotransform Flavanones into the Corresponding Flavones

by Monika Dymarska, Tomasz Janeczko and Edyta Kostrzewa-Susłow

Molecules 2020, 25(23), 5767; https://doi.org/10.3390/molecules25235767 - 7 Dec 2020

Cited by 6 | Viewed by 5849

Abstract

In vitro plant cultures are gaining in industrial importance, especially as biocatalysts and as sources of secondary metabolites used in pharmacy. The idea that guided us in our research was to evaluate the biocatalytic potential of newly obtained callus tissue towards flavonoid compounds. [...] Read more.

In vitro plant cultures are gaining in industrial importance, especially as biocatalysts and as sources of secondary metabolites used in pharmacy. The idea that guided us in our research was to evaluate the biocatalytic potential of newly obtained callus tissue towards flavonoid compounds. In this publication, we describe new ways of using callus cultures in the biotransformations. In the first method, the callus cultures grown on a solid medium are transferred to the water, the reaction medium into which the substrate is introduced. In the second method, biotransformation is carried out on a solid medium by growing callus cultures. In the course of the research, we have shown that the callus obtained from Phaseolus coccineus and Glycine max is capable of converting flavanone, 5-methoxyflavanone and 6-methoxyflavanone into the corresponding flavones. Full article

(This article belongs to the Special Issue Plant In Vitro Systems as an Effective Tool for In Vivo Biocatalysis of Bioactive Natural Products)

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17 pages, 5388 KiB

Open AccessArticle

Biodegradation of Poly (Butylene Succinate) (PBS)/Stearate Modified Magnesium-Aluminium Layered Double Hydroxide Composites under Marine Conditions Prepared via Melt Compounding

by Parameswaran Shaiju, Benamor-Bois Dorian, Ramsankar Senthamaraikannan and Ramesh Babu Padamati

Molecules 2020, 25(23), 5766; https://doi.org/10.3390/molecules25235766 - 7 Dec 2020

Cited by 21 | Viewed by 5371

Abstract

In the present work, polybutylene succinate (PBS)/stearate modified magnesium-aluminium layered double hydroxide (St-Mg-Al LDH) composites were prepared via melt processing and the effect of different loadings of St-Mg-Al LDH on the degradation behaviour of PBS under marine conditions was investigated. The morphological, mechanical [...] Read more.

In the present work, polybutylene succinate (PBS)/stearate modified magnesium-aluminium layered double hydroxide (St-Mg-Al LDH) composites were prepared via melt processing and the effect of different loadings of St-Mg-Al LDH on the degradation behaviour of PBS under marine conditions was investigated. The morphological, mechanical and thermal characteristics of the composites were studied using different characterisation techniques. Optical imaging and scanning electron microscopy revealed that the incorporation of St-Mg-Al LDH accelerates the degradation of PBS along with the activity of microorganisms adhered to the composite films. PBS/St-Mg-Al LDH composites are found to have lower thermal degradation temperatures than those of pure PBS. The decrease in thermal stability is correlated with the degradation of PBS due to the catalytic action Mg and Al present in LDH. Tensile and DMA analysis revealed that the addition of St-Mg-Al LDH did not have a significant impact on the mechanical properties of PBS. Full article

(This article belongs to the Special Issue Advanced Biodegradable Polymers)

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14 pages, 3024 KiB

Open AccessArticle

Towards a Non-Biased Formaldehyde Quantification in Leather: New Derivatization Conditions before HPLC Analysis of 2,4-Dinitrophenylhydrazine Derivatives

by Caroline Bourgeois, Nicolas Blanc, Jean-Claude Cannot and Claire Demesmay

Molecules 2020, 25(23), 5765; https://doi.org/10.3390/molecules25235765 - 7 Dec 2020

Cited by 8 | Viewed by 3491

Abstract

In leathers, formaldehyde is currently analyzed according to EN ISO 17226-1 standard, by reversed phase liquid chromatography after off-line precolumn derivatization with 2,4 dinitrophenylhydrazine (DNPH) in strong acidic conditions. We first demonstrate that this standard is not adapted to leather retanned with resins [...] Read more.

In leathers, formaldehyde is currently analyzed according to EN ISO 17226-1 standard, by reversed phase liquid chromatography after off-line precolumn derivatization with 2,4 dinitrophenylhydrazine (DNPH) in strong acidic conditions. We first demonstrate that this standard is not adapted to leather retanned with resins likely to release formaldehyde by hydrolysis. Indeed, formaldehyde content may be largely overestimated due to concomitant resin hydrolysis (in harsh acidic conditions) that releases formaldehyde during the derivatization step and during the waiting time on autosampler before analysis. Therefore, we thoroughly studied the derivatization step in order to propose new derivatization conditions. Replacing orthophosphoric acid by less acidic buffer solutions is not enough to avoid hydrolysis. A derivatization without adding acid is realized by solubilizing DNPH in acetonitrile instead of orthophosphoric acid. These conditions lead to a complete derivatization of formaldehyde in 3 h at 50 °C (in a water bath) while avoiding the hydrolysis of co-extracted dicyandiamide and melamine resins. The as-obtained leather extracts are stable over time. Formaldehyde contents found with this method agree with the formaldehyde content measured immediately at the end of derivatization reaction in standard conditions or with formaldehyde content measured by a home-designed flow injection analysis with acetylacetone online derivatization and UV detection. Full article

(This article belongs to the Section Analytical Chemistry)

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24 pages, 1468 KiB

Open AccessArticle

Developing a Library of Mannose-Based Mono- and Disaccharides: A General Chemoenzymatic Approach to Monohydroxylated Building Blocks

by Lisa Tanzi, Marina Simona Robescu, Sara Marzatico, Teresa Recca, Yongmin Zhang, Marco Terreni and Teodora Bavaro

Molecules 2020, 25(23), 5764; https://doi.org/10.3390/molecules25235764 - 7 Dec 2020

Cited by 10 | Viewed by 3596

Abstract

Regioselective deprotection of acetylated mannose-based mono- and disaccharides differently functionalized in anomeric position was achieved by enzymatic hydrolysis. Candida rugosa lipase (CRL) and Bacillus pumilus acetyl xylan esterase (AXE) were immobilized on octyl-Sepharose and glyoxyl-agarose, respectively. The regioselectivity of the biocatalysts was affected [...] Read more.

Regioselective deprotection of acetylated mannose-based mono- and disaccharides differently functionalized in anomeric position was achieved by enzymatic hydrolysis. Candida rugosa lipase (CRL) and Bacillus pumilus acetyl xylan esterase (AXE) were immobilized on octyl-Sepharose and glyoxyl-agarose, respectively. The regioselectivity of the biocatalysts was affected by the sugar structure and functionalization in anomeric position. Generally, CRL was able to catalyze regioselective deprotection of acetylated monosaccharides in C6 position. When acetylated disaccharides were used as substrates, AXE exhibited a marked preference for the C2, or C6 position when C2 was involved in the glycosidic bond. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monohydroxylated building blocks that could be used as intermediates for the synthesis of mannosylated glycoconjugate vaccines targeting mannose receptors of antigen presenting cells. Full article

(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates II)

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46 pages, 4618 KiB

Open AccessReview

Benefits and Detriments of Gadolinium from Medical Advances to Health and Ecological Risks

by Colin Unruh, Nicolas Van Bavel, Max Anikovskiy and Elmar J. Prenner

Molecules 2020, 25(23), 5762; https://doi.org/10.3390/molecules25235762 - 7 Dec 2020

Cited by 36 | Viewed by 8989

Abstract

Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data [...] Read more.

Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd³⁺ levels. Investigation of Gd³⁺ effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd³⁺ competes with calcium due to their similar size; other reports focus on interaction of Gd³⁺ with nucleic acids and carbohydrates. However, little is known about Gd³⁺ effects on membranes; yet some results suggest that Gd³⁺ interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd³⁺ on cell membrane organization that may lead to deleterious health consequences. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Hot Topics in Bioorganic Chemistry)

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19 pages, 5285 KiB

Open AccessArticle

Impact of Substitution Pattern and Chain Length on the Thermotropic Properties of Alkoxy-Substituted Triphenyl-Tristriazolotriazines

by Thorsten Rieth, Natalie Tober, Daniel Limbach, Tobias Haspel, Marcel Sperner, Niklas Schupp, Philipp Wicker, Stefan Glang, Matthias Lehmann and Heiner Detert

Molecules 2020, 25(23), 5761; https://doi.org/10.3390/molecules25235761 - 7 Dec 2020

Cited by 8 | Viewed by 4226

Abstract

Tristriazolotriazines (TTTs) with a threefold alkoxyphenyl substitution were prepared and studied by DSC, polarized optical microscopy (POM) and X-ray scattering. Six pentyloxy chains are sufficient to induce liquid-crystalline behavior in these star-shaped compounds. Thermotropic properties of TTTs with varying substitution patterns and a [...] Read more.

Tristriazolotriazines (TTTs) with a threefold alkoxyphenyl substitution were prepared and studied by DSC, polarized optical microscopy (POM) and X-ray scattering. Six pentyloxy chains are sufficient to induce liquid-crystalline behavior in these star-shaped compounds. Thermotropic properties of TTTs with varying substitution patterns and a periphery of linear chains of different lengths, branching in the chain and swallow-tails, are compared. Generally, these disks display broad and stable thermotropic mesophases, with the tangential TTT being superior to the radial isomer. The structure–property relationships of the number of alkyl chains, their position, length and structure were studied. Full article

(This article belongs to the Special Issue Liquid Crystals 2020)

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14 pages, 2834 KiB

Open AccessArticle

Euodia pasteuriana Methanol Extract Exerts Anti-Inflammatory Effects by Targeting TAK1 in the AP-1 Signaling Pathway

by Jianmei Zhang, Mi-Yeon Kim and Jae Youl Cho

Molecules 2020, 25(23), 5760; https://doi.org/10.3390/molecules25235760 - 7 Dec 2020

Cited by 4 | Viewed by 3048

Abstract

Euodia pasteuriana A. Chev. ex Guillaumin, also known as Melicope accedens (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although Euodia pasteuriana is used as a traditional medicine to treat a variety of inflammatory diseases, the pharmacological mechanisms related to [...] Read more.

Euodia pasteuriana A. Chev. ex Guillaumin, also known as Melicope accedens (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although Euodia pasteuriana is used as a traditional medicine to treat a variety of inflammatory diseases, the pharmacological mechanisms related to this plant are unclear. This study aimed to investigate the anti-inflammatory effects of a methanol extract of Euodia pasteuriana leaves (Ep-ME) on the production of inflammatory mediators, the mRNA expression of proinflammatory genes, and inflammatory signaling activities in macrophage cell lines. The results showed that Ep-ME strongly suppressed the release of nitric oxide (NO) in RAW264.7 cells induced with lipopolysaccharide (LPS), pam3CysSerLys4 (Pam3CSK), and polyinosinic-polycytidylic acid (poly I:C) without cytotoxicity. A reverse transcription-polymerase chain reaction further confirmed that Ep-ME suppressed the expression of interleukin 6 (IL-6), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-3 (MMP3), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP9) at the transcriptional level and reduced the luciferase activities of activator protein 1 (AP-1) reporter promoters. In addition, immunoblotting analyses of the whole lysate and nuclear fraction, as well as overexpression assays demonstrated that Ep-ME decreased the translocation of c-Jun and suppressed the activation of transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 signaling pathways. These results imply that Ep-ME could be developed as an anti-inflammatory agent that targets TAK1 in the AP-1 signaling pathway. Full article

(This article belongs to the Special Issue Plant Extracts: Immunomodulatory and Anti-cancer Properties)

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35 pages, 1796 KiB

Open AccessReview

Nanomaterials in Electrochemical Sensing Area: Applications and Challenges in Food Analysis

by Antonella Curulli

Molecules 2020, 25(23), 5759; https://doi.org/10.3390/molecules25235759 - 7 Dec 2020

Cited by 70 | Viewed by 5387

Abstract

Recently, nanomaterials have received increasing attention due to their unique physical and chemical properties, which make them of considerable interest for applications in many fields, such as biotechnology, optics, electronics, and catalysis. The development of nanomaterials has proven fundamental for the development of [...] Read more.

Recently, nanomaterials have received increasing attention due to their unique physical and chemical properties, which make them of considerable interest for applications in many fields, such as biotechnology, optics, electronics, and catalysis. The development of nanomaterials has proven fundamental for the development of smart electrochemical sensors to be used in different application fields such, as biomedical, environmental, and food analysis. In fact, they showed high performances in terms of sensitivity and selectivity. In this report, we present a survey of the application of different nanomaterials and nanocomposites with tailored morphological properties as sensing platforms for food analysis. Particular attention has been devoted to the sensors developed with nanomaterials such as carbon-based nanomaterials, metallic nanomaterials, and related nanocomposites. Finally, several examples of sensors for the detection of some analytes present in food and beverages, such as some hydroxycinnamic acids (caffeic acid, chlorogenic acid, and rosmarinic acid), caffeine (CAF), ascorbic acid (AA), and nitrite are reported and evidenced. Full article

(This article belongs to the Special Issue Exclusive Papers of the Editorial Board Members (EBMs) of the Materials Chemistry Section of Molecules)

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12 pages, 1224 KiB

Open AccessReview

Topical Administration of Terpenes Encapsulated in Nanostructured Lipid-Based Systems

by Elwira Lasoń

Molecules 2020, 25(23), 5758; https://doi.org/10.3390/molecules25235758 - 7 Dec 2020

Cited by 24 | Viewed by 4055

Abstract

Terpenes are a group of phytocompounds that have been used in medicine for decades owing to their significant role in human health. So far, they have been examined for therapeutic purposes as antibacterial, anti-inflammatory, antitumoral agents, and the clinical potential of this class [...] Read more.

Terpenes are a group of phytocompounds that have been used in medicine for decades owing to their significant role in human health. So far, they have been examined for therapeutic purposes as antibacterial, anti-inflammatory, antitumoral agents, and the clinical potential of this class of compounds has been increasing continuously as a source of pharmacologically interesting agents also in relation to topical administration. Major difficulties in achieving sustained delivery of terpenes to the skin are connected with their low solubility and stability, as well as poor cell penetration. In order to overcome these disadvantages, new delivery technologies based on nanostructures are proposed to improve bioavailability and allow controlled release. This review highlights the potential properties of terpenes loaded in several types of lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers) used to overcome free terpenes’ form limitations and potentiate their therapeutic properties for topical administration. Full article

(This article belongs to the Special Issue Terpenes and Terpene Derivatives)

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29 pages, 9080 KiB

Open AccessArticle

Physical, Thermal and Biological Properties of Yellow Dyes with Two Azodiphenylether Groups of Anthracene

by Carla Alice Carabet, Anca Moanță, Ion Pălărie, Gabriela Iacobescu, Andrei Rotaru, Marian Leulescu, Mariana Popescu and Petre Rotaru

Molecules 2020, 25(23), 5757; https://doi.org/10.3390/molecules25235757 - 6 Dec 2020

Cited by 9 | Viewed by 6325

Abstract

Two yellow bis-azo dyes containing anthracene and two azodiphenylether groups (BPA and BTA) were prepared, and an extensive investigation of their physical, thermal and biological properties was carried out. The chemical structure was confirmed by the FTIR spectra, while from the UV–Vis spectra, [...] Read more.

Two yellow bis-azo dyes containing anthracene and two azodiphenylether groups (BPA and BTA) were prepared, and an extensive investigation of their physical, thermal and biological properties was carried out. The chemical structure was confirmed by the FTIR spectra, while from the UV–Vis spectra, the quantum efficiency of the laser fluorescence at the 476.5 nm was determined to be 0.33 (BPA) and 0.50 (BTA). The possible transitions between the energy levels of the electrons of the chemical elements were established, identifying the energies and the electronic configurations of the levels of transition. Both crystals are anisotropic, the optical phenomenon of double refraction of polarized light (birefringence) taking place. Images of maximum illumination and extinction were recorded when the crystals of the bis-azo compounds rotated by 90° each, which confirms their birefringence. A morphologic study of the thin films deposited onto glass surfaces was performed, proving the good adhesion of both dyes. By thermal analysis and calorimetry, the melting temperatures were determined (~224–225 °C for both of them), as well as their decomposition pathways and thermal effects (enthalpy variations during undergoing processes); thus, good thermal stability was exhibited. The interaction of the two compounds with collagen in the suede was studied, as well as their antioxidant activity, advocating for good chemical stability and potential to be safely used as coloring agents in the food industry. Full article

(This article belongs to the Special Issue Colorants Changes during Food Treatment and Processing)

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19 pages, 7492 KiB

Open AccessArticle

Modulation of the Activity of Gold Clusters Immobilized on Functionalized Mesoporous Materials in the Oxidation of Cyclohexene via the Functional Group. The Case of Aminopropyl Moiety

by Ana Mato, Javier Agúndez, Carlos Márquez-Álvarez, Álvaro Mayoral and Joaquín Pérez-Pariente

Molecules 2020, 25(23), 5756; https://doi.org/10.3390/molecules25235756 - 6 Dec 2020

Cited by 5 | Viewed by 2439

Abstract

Gold nanoclusters and isolated gold atoms have been produced in a two-liquid phase procedure that involves a solution of gold in aqua regia and rosemary essential oil as organic layer. These gold entities have been immobilized on the ordered mesoporous silica material SBA-15 [...] Read more.

Gold nanoclusters and isolated gold atoms have been produced in a two-liquid phase procedure that involves a solution of gold in aqua regia and rosemary essential oil as organic layer. These gold entities have been immobilized on the ordered mesoporous silica material SBA-15 functionalized with different amounts of aminopropyl groups. The resulting materials have been characterized by XRD, N₂ adsorption, chemical analysis, TGA, ²⁹Si MAS NMR, ¹³C CP/MAS NMR, UV-vis spectroscopy, XPS, and STEM. The Au-containing materials retain the ordering and porosity of the pristine support. Gold content varies in the range of 0.07–0.7 wt% as a function of the specific immobilization conditions, while STEM evidences the presence of isolated gold atoms. XPS shows a shift of the Au 4f BE toward values lower than those of metallic gold. The catalytic activity in the oxidation of cyclohexene with molecular oxygen at atmospheric pressure parallels the Au content of the aminopropyl-SBA-15 supports. This activity is higher than that of analogous Au entities immobilized on SBA-15 functionalized with thiol or sulfonate groups, the activity decreasing in the order Au-NH₂ > Au-SO₃⁻ > Au-SH. This behavior has been attributed to differences in the interaction strength between the functional group and the Au entities, which is optimum for the aminopropyl groups. Full article

(This article belongs to the Special Issue Ordered Mesoporous Materials: New Developments in Synthesis, Characterization and Applications)

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27 pages, 1614 KiB

Open AccessReview

Nucleotide Sugars in Chemistry and Biology

by Satu Mikkola

Molecules 2020, 25(23), 5755; https://doi.org/10.3390/molecules25235755 - 6 Dec 2020

Cited by 67 | Viewed by 10394

Abstract

Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates. They are involved in processes that are targets for drug development, and their analogs are potential inhibitors of these processes. Drug [...] Read more.

Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates. They are involved in processes that are targets for drug development, and their analogs are potential inhibitors of these processes. Drug development requires efficient methods for the synthesis of oligosaccharides and nucleotide sugar building blocks as well as of modified structures as potential inhibitors. It requires also understanding the details of biological and chemical processes as well as the reactivity and reactions under different conditions. This article addresses all these issues by giving a broad overview on nucleotide sugars in biological and chemical reactions. As the background for the topic, glycosylation reactions in mammalian and bacterial cells are briefly discussed. In the following sections, structures and biosynthetic routes for nucleotide sugars, as well as the mechanisms of action of nucleotide sugar-utilizing enzymes, are discussed. Chemical topics include the reactivity and chemical synthesis methods. Finally, the enzymatic in vitro synthesis of nucleotide sugars and the utilization of enzyme cascades in the synthesis of nucleotide sugars and oligosaccharides are briefly discussed. Full article

(This article belongs to the Special Issue Nucleosides and Nucleotides)

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16 pages, 1943 KiB

Open AccessArticle

Co-Digestion of Grape Marc and Cheese Whey at High Total Solids Holds Potential for Sustained Bioenergy Generation

by Josue Kassongo, Esmaeil Shahsavari and Andrew S. Ball

Molecules 2020, 25(23), 5754; https://doi.org/10.3390/molecules25235754 - 6 Dec 2020

Cited by 6 | Viewed by 2284

Abstract

At the end of fermentation, wine contains approximately 20% (w/v) of solid material, known as grape marc (GM), produced at a yield of 2 t/ha. Cheese manufacture produces cheese whey (CW), which is over 80% of the processed milk, [...] Read more.

At the end of fermentation, wine contains approximately 20% (w/v) of solid material, known as grape marc (GM), produced at a yield of 2 t/ha. Cheese manufacture produces cheese whey (CW), which is over 80% of the processed milk, per unit volume. Both waste types represent an important fraction of the organic waste being disposed of by the wine and dairy industries. The objective of this study was to investigate the bioenergy potential through anaerobic codigestion of these waste streams. The best bioenergy profile was obtained from the digestion setups of mixing ratio 3/1 GM/CW (wet weight/wet weight). At this ratio, the inhibitory salinity of CW was sufficiently diluted, resulting in 23.73% conversion of the organic material to methane. On average, 64 days of steady bioenergy productivity was achieved, reaching a maximum of 85 ± 0.4% CH₄ purity with a maximum cumulative methane yield of 24.4 ± 0.11 L CH₄ kg⁻¹ VS. During the fermentation there was 18.63% CODt removal, 21.18% reduction of conductivity whilst salinity rose by 36.19%. It can be concluded that wine and dairy industries could utilise these waste streams for enhanced treatment and energy recovery, thereby developing a circular economy. Full article

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12 pages, 1166 KiB

Open AccessArticle

Development and Validation of High-Throughput Bioanalytical Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Quantification of Newly Synthesized Antitumor Carbonic Anhydrase Inhibitors in Human Plasma

by Ahmed M. Abdel-Megied, Wagdy M. Eldehna, Mohamed A. Abdelrahman and Fawzy A. Elbarbry

Molecules 2020, 25(23), 5753; https://doi.org/10.3390/molecules25235753 - 6 Dec 2020

Cited by 3 | Viewed by 3192

Abstract

In the present study, a sensitive and fully validated bioanalytical high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitative determination of three newly synthesized carbonic anhydrases inhibitors (CAIs) with potential antitumor activity in human plasma. The analytes and the [...] Read more.

In the present study, a sensitive and fully validated bioanalytical high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitative determination of three newly synthesized carbonic anhydrases inhibitors (CAIs) with potential antitumor activity in human plasma. The analytes and the internal standard (IS) were extracted using 1.5 mL acetonitrile from only 450 µL aliquots of human plasma to achieve the desired protein precipitation. Chromatographic separations were achieved on Phenomenex Kinetex^® C₁₈ column (100 × 4.6 mm, 2.6 µm) using a binary gradient elution mode with a run time of less than 6 min. The mobile phase consisted of solvent (A): 0.1% formic acid in 50% methanol and solvent B: 0.1% formic acid in acetonitrile (30:70, v/v), pumped at a flow rate of 0.8 mL/min. Detection was employed using triple quadrupole tandem mass spectrometer (API 3500) equipped with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was selected for quantitation through monitoring the precursor-to-parent ion transition at m/z 291.9 → 173.0, m/z 396.9 → 225.1, m/z 388.9 → 217.0, and m/z 146.9 → 91.0 for AW-9a, WES-1, WES-2, and Coumarin (IS), respectively. Linearity was computed using the weighted least-squares linear regression method (1/x²) over a concentration range of 1–1000, 2.5–800, and 5–500 ng/mL for AW-9a, WES-1, and WES-2; respectively. The bioanalytical LC-MS/MS method was fully validated as per U.S. Food and Drug Administration (FDA) guidelines with all respect to linearity, accuracy, precision, carry-over, selectivity, dilution integrity, and stability. The proposed LC-MS/MS method was applied successfully for the determination of all investigated drugs in spiked human plasma with no significant matrix effect, which is a crucial cornerstone in further therapeutic drug monitoring of newly developed therapeutic agents. Full article

(This article belongs to the Special Issue Analysis of Drugs in Biological Samples through Liquid Chromatography)

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9 pages, 1692 KiB

Open AccessArticle

Labeled vs. Label-Free Raman Imaging of Lipids in Endothelial Cells of Various Origins

by Basseem Radwan, Adriana Adamczyk, Szymon Tott, Krzysztof Czamara, Katarzyna Kaminska, Ewelina Matuszyk and Malgorzata Baranska

Molecules 2020, 25(23), 5752; https://doi.org/10.3390/molecules25235752 - 6 Dec 2020

Cited by 11 | Viewed by 4536

Abstract

Endothelial cells (EC) constitute a single layer of the lining of blood vessels and play an important role in maintaining cardiovascular homeostasis. Endothelial dysfunction has been recognized as a primary or secondary cause of many diseases and it manifests itself, among others, by [...] Read more.

Endothelial cells (EC) constitute a single layer of the lining of blood vessels and play an important role in maintaining cardiovascular homeostasis. Endothelial dysfunction has been recognized as a primary or secondary cause of many diseases and it manifests itself, among others, by increased lipid content or a change in the lipid composition in the EC. Therefore, the analysis of cellular lipids is crucial to understand the mechanisms of disease development. Tumor necrosis factor alpha (TNF-α)-induced inflammation of EC alters the lipid content of cells, which can be detected by Raman spectroscopy. By default, lipid detection is carried out in a label-free manner, and these compounds are recognized based on their spectral profile characteristics. We consider (3S,3′S)-astaxanthin (AXT), a natural dye with a characteristic resonance spectrum, as a new Raman probe for the detection of lipids in the EC of various vascular beds, i.e., the aorta, brain and heart. AXT colocalizes with lipids in cells, enabling imaging of lipid-rich cellular components in a time-dependent manner using laser power 10 times lower than that commonly used to measure biological samples. The results show that AXT can be used to study lipids distribution in EC at various locations, suggesting its use as a universal probe for studying cellular lipids using Raman spectroscopy. The use of labeled Raman imaging of lipids in the EC of various organs could contribute to their easier identification and to a better understanding of the development and progression of various vascular diseases, and it could also potentially improve their diagnosis and treatment. Full article

(This article belongs to the Special Issue Biomedical Applications of Infrared and Raman Spectroscopy)

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13 pages, 2760 KiB

Open AccessFeature PaperArticle

The Optimization of a Novel Hydrogel—Egg White-Alginate for 2.5D Tissue Engineering of Salivary Spheroid-Like Structure

by Yuli Zhang, Hieu M. Pham, Jose G. Munguia-Lopez, Joseph M. Kinsella and Simon D. Tran

Molecules 2020, 25(23), 5751; https://doi.org/10.3390/molecules25235751 - 6 Dec 2020

Cited by 19 | Viewed by 5068

Abstract

Hydrogels have been used for a variety of biomedical applications; in tissue engineering, they are commonly used as scaffolds to cultivate cells in a three-dimensional (3D) environment allowing the formation of organoids or cellular spheroids. Egg white-alginate (EWA) is a novel hydrogel which [...] Read more.

Hydrogels have been used for a variety of biomedical applications; in tissue engineering, they are commonly used as scaffolds to cultivate cells in a three-dimensional (3D) environment allowing the formation of organoids or cellular spheroids. Egg white-alginate (EWA) is a novel hydrogel which combines the advantages of both egg white and alginate; the egg white material provides extracellular matrix (ECM)-like proteins that can mimic the ECM microenvironment, while alginate can be tuned mechanically through its ionic crosslinking property to modify the scaffold’s porosity, strength, and stiffness. In this study, a frozen calcium chloride (CaCl₂) disk technique to homogenously crosslink alginate and egg white hydrogel is presented for 2.5D culture of human salivary cells. Different EWA formulations were prepared and biologically evaluated as a spheroid-like structure platform. Although all five EWA hydrogels showed biocompatibility, the EWA with 1.5% alginate presented the highest cell viability, while EWA with 3% alginate promoted the formation of larger size salivary spheroid-like structures. Our EWA hydrogel has the potential to be an alternative 3D culture scaffold that can be used for studies on drug-screening, cell migration, or as an in vitro disease model. In addition, EWA can be used as a potential source for cell transplantation (i.e., using this platform as an ex vivo environment for cell expansion). The low cost of producing EWA is an added advantage. Full article

(This article belongs to the Special Issue Hydrogels for Tissue Engineering and Regenerative Medicine)

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13 pages, 2958 KiB

Open AccessArticle

Fe(III) Complexes Based on Mono- and Bis-pyrazolyl-s-triazine Ligands: Synthesis, Molecular Structure, Hirshfeld, and Antimicrobial Evaluations

by Saied M. Soliman, Hessa H. Al-Rasheed, Jörg H. Albering and Ayman El-Faham

Molecules 2020, 25(23), 5750; https://doi.org/10.3390/molecules25235750 - 5 Dec 2020

Cited by 16 | Viewed by 2703

Abstract

The self-assembly of iron(III) chloride with three pyrazolyl-s-triazine ligands, namely 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazine (^PipBPT), 4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine (^MorphBPT), and 4,4’-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine (^bisMorphPT) afforded [Fe(^PipBPT)Cl₂][FeCl₄] ( [...] Read more.

The self-assembly of iron(III) chloride with three pyrazolyl-s-triazine ligands, namely 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazine (^PipBPT), 4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine (^MorphBPT), and 4,4’-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine (^bisMorphPT) afforded [Fe(^PipBPT)Cl₂][FeCl₄] (1), [Fe(^MorphBPT)Cl₂][FeCl₄] (2), and [H(^bisMorphPT)][FeCl₄]. ^bisMorphPT.2H₂O (3), respectively, in good yield. In complexes 1 and 2, the Fe(III) is pentacoordinated with three Fe-N interactions from the pincer ligand and two coordinated chloride anions in the inner sphere, and FeCl₄¯ in the outer sphere. Complex 3 is comprised of one protonated ligand as cationic part, one FeCl₄¯ anion, and one neutral ^bisMorphPT molecule in addition to two crystallized water molecules. Analysis of molecular packing using Hirshfeld calculations indicated that H…H and Cl…H are the most important in the molecular packing. They comprised 40.1% and 37.4%, respectively in 1 and 32.4% and 37.8%, respectively in 2. Complex 1 exhibited the most bioactivity against the tested microbes while 3 had the lowest bioactivity. The ^bisMorphPT and ^MorphBPT were inactive towards the tested microbes while ^PipBPT was active. As a whole, the Fe(III) complexes have enhanced antibacterial and antifungal activities as compared to the free ligands. Full article

(This article belongs to the Special Issue Recent Advances in the Synthesis, Functionalization and Applications of Pyrazole-Type Compounds I)

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27 pages, 2337 KiB

Open AccessArticle

Detection of Fungi and Oomycetes by Volatiles Using E-Nose and SPME-GC/MS Platforms

by Jérémie Loulier, François Lefort, Marcin Stocki, Monika Asztemborska, Rafał Szmigielski, Krzysztof Siwek, Tomasz Grzywacz, Tom Hsiang, Sławomir Ślusarski, Tomasz Oszako, Marcin Klisz, Rafał Tarakowski and Justyna Anna Nowakowska

Molecules 2020, 25(23), 5749; https://doi.org/10.3390/molecules25235749 - 5 Dec 2020

Cited by 42 | Viewed by 6036

Abstract

Fungi and oomycetes release volatiles into their environment which could be used for olfactory detection and identification of these organisms by electronic-nose (e-nose). The aim of this study was to survey volatile compound emission using an e-nose device and to identify released molecules [...] Read more.

Fungi and oomycetes release volatiles into their environment which could be used for olfactory detection and identification of these organisms by electronic-nose (e-nose). The aim of this study was to survey volatile compound emission using an e-nose device and to identify released molecules through solid phase microextraction–gas chromatography/mass spectrometry (SPME–GC/MS) analysis to ultimately develop a detection system for fungi and fungi-like organisms. To this end, cultures of eight fungi (Armillaria gallica, Armillaria ostoyae, Fusarium avenaceum, Fusarium culmorum, Fusarium oxysporum, Fusarium poae, Rhizoctonia solani, Trichoderma asperellum) and four oomycetes (Phytophthora cactorum, P. cinnamomi, P. plurivora, P. ramorum) were tested with the e-nose system and investigated by means of SPME-GC/MS. Strains of F. poae, R. solani and T. asperellum appeared to be the most odoriferous. All investigated fungal species (except R. solani) produced sesquiterpenes in variable amounts, in contrast to the tested oomycetes strains. Other molecules such as aliphatic hydrocarbons, alcohols, aldehydes, esters and benzene derivatives were found in all samples. The results suggested that the major differences between respective VOC emission ranges of the tested species lie in sesquiterpene production, with fungi emitting some while oomycetes released none or smaller amounts of such molecules. Our e-nose system could discriminate between the odors emitted by P. ramorum, F. poae, T. asperellum and R. solani, which accounted for over 88% of the PCA variance. These preliminary results of fungal and oomycete detection make the e-nose device suitable for further sensor design as a potential tool for forest managers, other plant managers, as well as regulatory agencies such as quarantine services. Full article

(This article belongs to the Special Issue Discovery of Bioactive Ingredients from Natural Products)

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15 pages, 1540 KiB

Open AccessCommunication

Synthesis of (Het)aryl 2-(2-hydroxyaryl)cyclopropyl Ketones

by Alexander A. Fadeev, Alexey O. Chagarovskiy, Anton S. Makarov, Irina I. Levina, Olga A. Ivanova, Maxim G. Uchuskin and Igor V. Trushkov

Molecules 2020, 25(23), 5748; https://doi.org/10.3390/molecules25235748 - 5 Dec 2020

Cited by 3 | Viewed by 4188

Abstract

A simple general method for the synthesis of 1-acyl-2-(ortho-hydroxyaryl)cyclopropanes, which belong to the donor–acceptor cyclopropane family, has been developed. This method, based on the Corey–Chaykovsky cyclopropanation of 2-hydroxychalcones, allows for the preparation of a large diversity of hydroxy-substituted cyclopropanes, which can [...] Read more.

A simple general method for the synthesis of 1-acyl-2-(ortho-hydroxyaryl)cyclopropanes, which belong to the donor–acceptor cyclopropane family, has been developed. This method, based on the Corey–Chaykovsky cyclopropanation of 2-hydroxychalcones, allows for the preparation of a large diversity of hydroxy-substituted cyclopropanes, which can serve as promising building blocks for the synthesis of various bioactive compounds. Full article

(This article belongs to the Special Issue Advances in Organic Synthesis: A Theme Issue in Honor of Professor Mieczysław Mąkosza)

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