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Molecules, Volume 28, Issue 4 (February-2 2023) – 484 articles

Cover Story (view full-size image): The complexation abilities of cucurbiturils (CBs) could be enhanced with the assistance of metal cations, which can exert a dual effect on the complexation process: either by competitively binding to the host entity or cooperatively associating to the CB[n]-guest structures. The current study focuses on the role of two metal species (Mg2+ and Ga3+) in the complex formation of CBs with three dye molecules: Thiazole Orange, Neutral Red, and Thioflavin T. Various key factors influencing the process have been recognized such as the pH and dielectric constant of the medium, cavity size of the host, Mn+ charge, and presence/absence of hydration shell around the metal cation. The results obtained from density functional theory (DFT) calculations shed new light on several aspects of the cucurbituril complexation chemistry. View this paper
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26 pages, 6377 KiB  
Review
Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases
Molecules 2023, 28(4), 2000; https://doi.org/10.3390/molecules28042000 - 20 Feb 2023
Cited by 2 | Viewed by 2944
Abstract
A comprehensive understanding of the mechanisms involved in epigenetic changes in gene expression is essential to the clinical management of diseases linked to the SMYD family of lysine methyltransferases. The five known SMYD enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine [...] Read more.
A comprehensive understanding of the mechanisms involved in epigenetic changes in gene expression is essential to the clinical management of diseases linked to the SMYD family of lysine methyltransferases. The five known SMYD enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine (SAM) to specific lysines on histones and non-histone substrates. SMYDs family members have distinct tissue distributions and tissue-specific functions, including regulation of development, cell differentiation, and embryogenesis. Diseases associated with SMYDs include the repressed transcription of SMYD1 genes needed for the formation of ion channels in the heart leading to heart failure, SMYD2 overexpression in esophageal squamous cell carcinoma (ESCC) or p53-related cancers, and poor prognosis associated with SMYD3 overexpression in more than 14 types of cancer including breast cancer, colon cancer, prostate cancer, lung cancer, and pancreatic cancer. Given the importance of epigenetics in various pathologies, the development of epigenetic inhibitors has attracted considerable attention from the pharmaceutical industry. The pharmacologic development of the inhibitors involves the identification of molecules regulating both functional SMYD SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domains, a process facilitated by available X-ray structures for SMYD1, SMYD2, and SMYD3. Important leads for potential pharmaceutical agents have been reported for SMYD2 and SMYD3 enzymes, and six epigenetic inhibitors have been developed for drugs used to treat myelodysplastic syndrome (Vidaza, Dacogen), cutaneous T-cell lymphoma (Zoinza, Isrodax), and peripheral T-cell lymphoma (Beleodag, Epidaza). The recently demonstrated reversal of SMYD histone methylation suggests that reversing the epigenetic effects of SMYDs in cancerous tissues may be a desirable target for pharmacological development. Full article
(This article belongs to the Special Issue Exploring Bioactive Organic Compounds for Drug Discovery)
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15 pages, 5016 KiB  
Article
Femtosecond Time-Resolved Observation of Relaxation and Wave Packet Dynamics of the S1 State in Electronically Excited o-Fluoroaniline
Molecules 2023, 28(4), 1999; https://doi.org/10.3390/molecules28041999 - 20 Feb 2023
Viewed by 1385
Abstract
Quantum beat frequency is the basis for understanding interference effects and vibrational wave packet dynamics and has important applications. Using femtosecond time-resolved mass spectrometry and femtosecond time-resolved photoelectron image combined with theoretical calculations, we study the electronic excited-state relaxation of o-fluoraniline molecule [...] Read more.
Quantum beat frequency is the basis for understanding interference effects and vibrational wave packet dynamics and has important applications. Using femtosecond time-resolved mass spectrometry and femtosecond time-resolved photoelectron image combined with theoretical calculations, we study the electronic excited-state relaxation of o-fluoraniline molecule and the time-dependent evolution of vibrational wave packets between different eigenstates. After the molecule absorbs a photon of 288.3 nm and is excited to the S1 state, intramolecular vibrational redistribution first occurs on the time scale τ1 = 349 fs, and then the transition to the triplet state occurs through the intersystem crossing on the time scale τ2 = 583 ps, and finally, the triplet state occurs decays slowly through the time scale τ3 = 2074 ps. We find the intramolecular vibrational redistribution is caused by the 00, 10b1 and 16a1 vibrational modes of the Sl state origin. That is, the 288.3 nm femtosecond laser excites the molecule to the S1 state, and the continuous flow of the vibrational wave packet prepares a coherent superposition state of three vibrational modes. Through extracting the oscillation of different peak intensities in the photoelectron spectrum, we observe reversible changes caused by mutual interference of the S1 00, S1 10b1 and S1 16a1 states when the wave packets flow. When the pump pulse is 280 nm, the beat frequency disappears completely. This is explained in terms of increases in the vibrational field density and characteristic period of oscillation, and statistical averaging makes the quantum effect smooth and indistinguishable. In addition, the Rydberg component of the S1 state is more clearly resolved by combining experiment and theory. Full article
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35 pages, 6797 KiB  
Review
Synthesis and Application Dichalcogenides as Radical Reagents with Photochemical Technology
Molecules 2023, 28(4), 1998; https://doi.org/10.3390/molecules28041998 - 20 Feb 2023
Cited by 4 | Viewed by 2202
Abstract
Dichalcogenides (disulfides and diselenides), as reactants for organic transformations, are important and widely used because of their potential to react with nucleophiles, electrophilic reagents, and radical precursors. In recent years, in combination with photochemical technology, the application of dichalcogenides as stable radical reagents [...] Read more.
Dichalcogenides (disulfides and diselenides), as reactants for organic transformations, are important and widely used because of their potential to react with nucleophiles, electrophilic reagents, and radical precursors. In recent years, in combination with photochemical technology, the application of dichalcogenides as stable radical reagents has opened up a new route to the synthesis of various sulfur- and selenium-containing compounds. In this paper, synthetic strategies for disulfides and diselenides and their applications with photochemical technology are reviewed: (i) Cyclization of dichalcogenides with alkenes and alkynes; (ii) direct selenylation/sulfuration of C−H/C−C/C−N bonds; (iii) visible-light-enabled seleno- and sulfur-bifunctionalization of alkenes/alkynes; and (iv) Direct construction of the C(sp)–S bond. In addition, the scopes, limitations, and mechanisms of some reactions are also described. Full article
(This article belongs to the Special Issue Synthesis and Modification of Nitrogen Heterocyclic Compounds)
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26 pages, 5685 KiB  
Article
Synthesis of New Amino-Functionalized Porphyrins:Preliminary Study of Their Organophotocatalytic Activity
Molecules 2023, 28(4), 1997; https://doi.org/10.3390/molecules28041997 - 20 Feb 2023
Cited by 2 | Viewed by 2165
Abstract
The design, synthesis, and initial study of amino-functionalized porphyrins as a new class of bifunctional catalysts for asymmetric organophotocatalysis is described. Two new types of amine–porphyrin hybrids derived from 5,10,15,20-tetraphenylporphyrin (TPPH2), in which a cyclic secondary amine moiety is covalently linked [...] Read more.
The design, synthesis, and initial study of amino-functionalized porphyrins as a new class of bifunctional catalysts for asymmetric organophotocatalysis is described. Two new types of amine–porphyrin hybrids derived from 5,10,15,20-tetraphenylporphyrin (TPPH2), in which a cyclic secondary amine moiety is covalently linked either to a β-pyrrolic position (Type A) or to the p-position of one of the meso phenyl groups (Type B), were prepared by condensation, reductive amination, or amidation reactions from the suitable porphyrins (either formyl or methanamine derivatives) with readily available chiral amines. A preliminary study of the possible use of Type A amine–porphyrin hybrids as asymmetric, bifunctional organophotocatalysts was performed using the chiral, imidazolidinone-catalyzed Diels–Alder cycloaddition between cyclopentadiene 28 and trans-cinnamaldehyde 29 as a benchmark reaction. The yield and the stereochemical outcome of this process, obtained under purely organocatalytic conditions, under dual organophocatalysis, and under bifunctional organophotocatalysis, were compared. Full article
(This article belongs to the Special Issue Porphyrin-Based Compounds: Synthesis and Application)
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21 pages, 2820 KiB  
Article
From Aquaculture to Aquaculture: Production of the Fish Feed Additive Astaxanthin by Corynebacterium glutamicum Using Aquaculture Sidestream
Molecules 2023, 28(4), 1996; https://doi.org/10.3390/molecules28041996 - 20 Feb 2023
Cited by 6 | Viewed by 2271
Abstract
Circular economy holds great potential to minimize the use of finite resources, and reduce waste formation by the creation of closed-loop systems. This also pertains to the utilization of sidestreams in large-scale biotechnological processes. A flexible feedstock concept has been established for the [...] Read more.
Circular economy holds great potential to minimize the use of finite resources, and reduce waste formation by the creation of closed-loop systems. This also pertains to the utilization of sidestreams in large-scale biotechnological processes. A flexible feedstock concept has been established for the industrially relevant Corynebacterium glutamicum, which naturally synthesizes the yellow C50 carotenoid decaprenoxanthin. In this study, we aimed to use a preprocessed aquaculture sidestream for production of carotenoids, including the fish feed ingredient astaxanthin by C. glutamicum. The addition of a preprocessed aquaculture sidestream to the culture medium did not inhibit growth, obviated the need for addition of several components of the mineral salt’s medium, and notably enhanced production of astaxanthin by an engineered C. glutamicum producer strain. Improved astaxanthin production was scaled to 2 L bioreactor fermentations. This strategy to improve astaxanthin production was shown to be transferable to production of several native and non-native carotenoids. Thus, this study provides a proof-of-principle for improving carotenoid production by C. glutamicum upon supplementation of a preprocessed aquaculture sidestream. Moreover, in the case of astaxanthin production it may be a potential component of a circular economy in aquaculture. Full article
(This article belongs to the Section Green Chemistry)
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17 pages, 4273 KiB  
Article
OAT3 Participates in Drug–Drug Interaction between Bentysrepinine and Entecavir through Interactions with M8—A Metabolite of Bentysrepinine—In Rats and Humans In Vitro
Molecules 2023, 28(4), 1995; https://doi.org/10.3390/molecules28041995 - 20 Feb 2023
Cited by 2 | Viewed by 1396
Abstract
Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and [...] Read more.
Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and potential drug–drug interactions (DDIs) remain unclear. The present study aimed to determine the organic anion transporters (OATs) involved in the renal disposition of Y101 and to predict the potential DDI between Y101 and entecavir, the first-line agent against HBV and a substrate of OAT1/3. Pharmacokinetic studies and uptake assays using rat kidney slices, as well as hOAT1/3-HEK293 cells, were performed to evaluate potential DDI. The co-administration of probenecid (an inhibitor of OATs) significantly increased the plasma concentrations and area under the plasma concentration–time curves of M8 and M9 but not Y101, while reduced renal clearance and the cumulative urinary excretion of M8 were observed in rats. The time course of Y101 and M8 uptake via rat kidney slices was temperature-dependent. Moreover, the uptake of M8 was inhibited significantly by probenecid and benzylpenicillin, but not by p-aminohippurate or tetraethyl ammonium. M8 was found to be a substrate of hOAT3, but Y101 is not a substrate of either hOAT1 or hOAT3. Additionally, the entecavir inhibited the uptake of M8 in the hOAT3-transfected cells and rat kidney slices in vitro. Interestingly, no significant changes were observed in the pharmacokinetic parameters of Y101, M8 or entecavir, regardless of intravenous or oral co-administration of Y101 and entecavir in rats. In conclusion, M8 is a substrate of OAT3 in rats and humans. Furthermore, M8 also mediates the DDI between Y101 and entecavir in vitro, mediated by OAT3. We speculate that it would be safe to use Y101 with entecavir in clinical practice. Our results provide useful information with which to predict the DDIs between Y101 and other drugs that act as substrates of OAT3. Full article
(This article belongs to the Special Issue New Advances in Drug Metabolism and Pharmacokinetics)
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12 pages, 1892 KiB  
Communication
Low-Coordinate Mixed Ligand NacNac Complexes of Rare Earth Metals
Molecules 2023, 28(4), 1994; https://doi.org/10.3390/molecules28041994 - 20 Feb 2023
Cited by 1 | Viewed by 1608
Abstract
We report the synthesis and characterization of two types of new mixed-ligand rare earth complexes: tetracoordinate (NacNacMes)Ln(BIANdipp) (Ln = Dy (1), Er (2) and Y (3)) and pentacoordinate (NacNacMes)Ln(APdipp)(THF) [...] Read more.
We report the synthesis and characterization of two types of new mixed-ligand rare earth complexes: tetracoordinate (NacNacMes)Ln(BIANdipp) (Ln = Dy (1), Er (2) and Y (3)) and pentacoordinate (NacNacMes)Ln(APdipp)(THF) (Ln = Dy (4), Er (5) and Y (6)). The first three compounds were prepared by the reaction of [(BIANDipp)LnI] with potassium β-diketiminate. The salt metathesis of β-diketiminato-supported rare earth dichlorides (NacNacMes)LnCl2(THF)2 with sodium o-amidophenolate results in compounds 46. The crystal structures of complexes 16 were determined by single-crystal analysis. The combination of bulky monoanionic N-mesityl-substituted β-diketiminates with sterically hindered redox-active ligands led to the very low coordination numbers of rare earths and strong distortion of the chelate ligands. Full article
(This article belongs to the Special Issue Molecules in 2023)
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17 pages, 4520 KiB  
Article
Flow-Based Fmoc-SPPS Preparation and SAR Study of Cathelicidin-PY Reveals Selective Antimicrobial Activity
Molecules 2023, 28(4), 1993; https://doi.org/10.3390/molecules28041993 - 20 Feb 2023
Cited by 5 | Viewed by 2030
Abstract
Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH2-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog Paa yunnanensis (PY) and reported to possess broad-spectrum antibacterial [...] Read more.
Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH2-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog Paa yunnanensis (PY) and reported to possess broad-spectrum antibacterial and antifungal properties, exhibiting low cytotoxic and low hemolytic activity. Herein, we detail the total synthesis of cathelicidin-PY using an entirely on-resin synthesis, including assembly of the linear sequence by rapid flow Fmoc-SPPS and iodine-mediated disulfide bridge formation. By optimising a synthetic strategy to prepare cathelicidin-PY, this strategy was subsequently adapted to prepare a bicyclic head-to-tail cyclised derivative of cathelicidin-PY. The structure-activity relationship (SAR) of cathelicidin-PY with respect to the N-terminally positioned disulfide was further probed by preparing an alanine-substituted linear analogue and a series of lactam-bridged peptidomimetics implementing side chain to side chain cyclisation. The analogues were investigated for antimicrobial activity, secondary structure by circular dichroism (CD), and stability in human serum. Surprisingly, the disulfide bridge emerged as non-essential to antimicrobial activity and secondary structure but was amenable to synthetic modification. Furthermore, the synthetic AMP and multiple analogues demonstrated selective activity towards Gram-negative pathogen E. coli in physiologically relevant concentrations of divalent cations. Full article
(This article belongs to the Special Issue Advances in Research of Short Peptides II)
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18 pages, 4616 KiB  
Article
Impact of Sample Preparation Methods on Single-Cell X-ray Microscopy and Light Elemental Analysis Evaluated by Combined Low Energy X-ray Fluorescence, STXM and AFM
Molecules 2023, 28(4), 1992; https://doi.org/10.3390/molecules28041992 - 20 Feb 2023
Cited by 3 | Viewed by 1481
Abstract
Background: Although X-ray fluorescence microscopy is becoming a widely used technique for single-cell analysis, sample preparation for this microscopy remains one of the main challenges in obtaining optimal conditions for the measurements in the X-ray regime. The information available to researchers on sample [...] Read more.
Background: Although X-ray fluorescence microscopy is becoming a widely used technique for single-cell analysis, sample preparation for this microscopy remains one of the main challenges in obtaining optimal conditions for the measurements in the X-ray regime. The information available to researchers on sample treatment is inadequate and unclear, sometimes leading to wasted time and jeopardizing the experiment’s success. Many cell fixation methods have been described, but none of them have been systematically tested and declared the most suitable for synchrotron X-ray microscopy. Methods: The HEC-1-A endometrial cells, human spermatozoa, and human embryonic kidney (HEK-293) cells were fixed with organic solvents and cross-linking methods: 70% ethanol, 3.7%, and 2% paraformaldehyde; in addition, HEK-293 cells were subjected to methanol/ C3H6O treatment and cryofixation. Fixation methods were compared by coupling low-energy X-ray fluorescence with scanning transmission X-ray microscopy and atomic force microscopy. Results: Organic solvents lead to greater dehydration of cells, which has the most significant effect on the distribution and depletion of diffusion elements. Paraformaldehyde provides robust and reproducible data. Finally, the cryofixed cells provide the best morphology and element content results. Conclusion: Although cryofixation seems to be the most appropriate method as it allows for keeping cells closer to physiological conditions, it has some technical limitations. Paraformaldehyde, when used at the average concentration of 3.7%, is also an excellent alternative for X-ray microscopy. Full article
(This article belongs to the Special Issue Recent Advances and Future Trends in Sample Preparation II)
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19 pages, 5104 KiB  
Review
Recent Progress in Vacuum Engineering of Ionic Liquids
Molecules 2023, 28(4), 1991; https://doi.org/10.3390/molecules28041991 - 20 Feb 2023
Cited by 1 | Viewed by 1472
Abstract
Since the discovery of ionic liquids (ILs) as a new class of liquid that can survive in a vacuum at room temperature, they have been aimed at being characterized with vacuum analysis techniques and used in vacuum processes for the last two decades. [...] Read more.
Since the discovery of ionic liquids (ILs) as a new class of liquid that can survive in a vacuum at room temperature, they have been aimed at being characterized with vacuum analysis techniques and used in vacuum processes for the last two decades. In this review, our state-of-the-art of the vacuum engineering of ILs will be introduced. Beginning with nanoscale vacuum deposition of IL films and their thickness-dependent ionic conductivity, there are presented some new applications of the ellipsometry to in situ monitoring of the thickness of IL films and their glass transitions, and of the surface thermal fluctuation spectroscopy to investigation of the rheological properties of IL films. Furthermore, IL-VLS (vapor-liquid-solid) growth, a vacuum deposition via IL, has been found successful, enhancing the crystallinity of vacuum-deposited crystals and films, and sometimes controlling their surface morphology and polymorphs. Among recent applications of ILs are the use of metal ions-containing IL and thin film nano IL gel. The former is proposed as a low temperature evaporation source of metals, such as Ta, in vacuum deposition, while the latter is demonstrated to work as a gate electrolyte in an electric double layer organic transistor. Full article
(This article belongs to the Special Issue Properties and Applications of Ionic Liquids-Based Advanced Materials)
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19 pages, 700 KiB  
Review
Renoprotective Effects of Tanshinone IIA: A Literature Review
Molecules 2023, 28(4), 1990; https://doi.org/10.3390/molecules28041990 - 20 Feb 2023
Cited by 6 | Viewed by 2361
Abstract
The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid–base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by [...] Read more.
The kidney is an important organ in the human body, with functions such as urine production, the excretion of metabolic waste, the regulation of water, electrolyte and acid–base balance and endocrine release. The morbidity and mortality of kidney diseases are increasing year by year worldwide, and they have become a serious public health problem. In recent years, natural products derived from fungi, plants and animals have become an important alternative source of treatment for kidney diseases because of their multiple pathways, multiple targets, safety, low toxicity and few side effects. Tanshinone IIA (Tan IIA) is a lipid-soluble diterpene quinone isolated from the Chinese herb Salvia miltiorrhiza, considered as a common drug for the treatment of cardiovascular diseases. As researchers around the world continue to explore its unknown biological activities, it has also been found to have a wide range of biological effects, such as anti-cancer, anti-oxidative stress, anti-inflammatory, anti-fibrotic, and hepatoprotective effects, among others. In recent years, many studies have elaborated on its renoprotective effects in various renal diseases, including diabetic nephropathy (DN), renal fibrosis (RF), uric acid nephropathy (UAN), renal cell carcinoma (RCC) and drug-induced kidney injury caused by cisplatin, vancomycin and acetaminophen (APAP). These effects imply that Tan IIA may be a promising drug to use against renal diseases. This article provides a comprehensive review of the pharmacological mechanisms of Tan IIA in the treatment of various renal diseases, and it provides some references for further research and clinical application of Tan IIA in renal diseases. Full article
(This article belongs to the Section Natural Products Chemistry)
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16 pages, 15552 KiB  
Article
Chemical Profiling, Bioactive Properties, and Anticancer and Antimicrobial Potential of Juglans regia L. Leaves
Molecules 2023, 28(4), 1989; https://doi.org/10.3390/molecules28041989 - 20 Feb 2023
Cited by 8 | Viewed by 1864
Abstract
The aim of this study was to assess the biological potential of the polyphenolic fraction isolated from J. regia leaves, collected in the Subcarpathian region (Poland). The phenolic profile was determined using the UPLC-PDA-MS/MS method. Biological activity was determined by evaluating the antioxidant, [...] Read more.
The aim of this study was to assess the biological potential of the polyphenolic fraction isolated from J. regia leaves, collected in the Subcarpathian region (Poland). The phenolic profile was determined using the UPLC-PDA-MS/MS method. Biological activity was determined by evaluating the antioxidant, anticancer, antibacterial, and antifungal effects. Prior to this study, the purified polyphenolic fraction was not been tested in this regard. A total of 40 phenolic compounds (104.28 mg/g dw) were identified, with quercetin 3-O-glucoside and quercetin pentosides dominating. The preparation was characterized by a high ability to chelate iron ions and capture O2•− and OH radicals (reaching IC50 values of 388.61, 67.78 and 193.29 µg/mL, respectively). As for the anticancer activity, among the six tested cell lines, the preparation reduced the viability of the DLD-1, Caco-2, and MCF-7 lines the most, while in the antibacterial activity, among the seven tested strains, the highest susceptibility has been demonstrated against K. pneumoniae, S. pyogenes, and S. aureus. Depending on the needs, such a preparation can be widely used in the design of functional food and/or the cosmetics industry. Full article
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17 pages, 4211 KiB  
Article
Manipulation in Culture Conditions of Nanofrustulum shiloi for Enhanced Fucoxanthin Production and Isolation by Preparative Chromatography
Molecules 2023, 28(4), 1988; https://doi.org/10.3390/molecules28041988 - 20 Feb 2023
Cited by 3 | Viewed by 1605
Abstract
Microalgae produce a variety of high-value chemicals including carotenoids. Fucoxanthin is also a carotenoid that has many physiological functions and biological properties. For this reason, the cost-effective production of fucoxanthin at an industrial scale has gained significant attention. In the proposed study, fucoxanthin [...] Read more.
Microalgae produce a variety of high-value chemicals including carotenoids. Fucoxanthin is also a carotenoid that has many physiological functions and biological properties. For this reason, the cost-effective production of fucoxanthin at an industrial scale has gained significant attention. In the proposed study, fucoxanthin production was aimed to be increased by altering the culture conditions of N. shiloi. The effect of light intensity aeration rate, different nitrogen sources, and oxidative stress on the biomass and fucoxanthin productivity have been discussed. Based on these results, the fucoxanthin increased to 97.45 ± 2.64 mg/g by adjusting the light intensity to 50 µmol/m2s, and aeration rate at 5 L/min using oxidative stress through the addition of 0.1 mM H2O2 and 0.1 mM NaOCl to the culture medium. Fucoxanthin was then purified with preparative HPLC using C30 carotenoid column (10 mm × 250 mm, 5 μm). After the purification procedure, Liquid chromatography tandem mass spectrometry (LC–MS/MS) and UV-vis spectroscopy were employed for the confirmation of fucoxanthin. This study presented a protocol for obtaining and purifying considerable amounts of biomass and fucoxanthin from diatom by manipulating culture conditions. With the developed methodology, N. shiloi could be evaluated as a promising source of fucoxanthin at the industrial scale for food, feed, cosmetic, and pharmaceutical industries. Full article
(This article belongs to the Section Analytical Chemistry)
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16 pages, 2477 KiB  
Article
Design, Synthesis, and Pharmacology of New Triazole-Containing Quinolinones as CNS Active Agents
Molecules 2023, 28(4), 1987; https://doi.org/10.3390/molecules28041987 - 20 Feb 2023
Cited by 1 | Viewed by 1441
Abstract
Epilepsy and major depressive disorder are the two of the most common central nervous system (CNS) diseases. Clinicians and patients call for new antidepressants, antiseizure medicines, and in particular drugs for depression and epilepsy comorbidities. In this work, a dozen new triazole-quinolinones were [...] Read more.
Epilepsy and major depressive disorder are the two of the most common central nervous system (CNS) diseases. Clinicians and patients call for new antidepressants, antiseizure medicines, and in particular drugs for depression and epilepsy comorbidities. In this work, a dozen new triazole-quinolinones were designed, synthesized, and investigated as CNS active agents. All compounds reduced the immobility time significantly during the forced swim test (FST) in mice at the dosage of 50 mg/kg. Compounds 3f3j gave superior performance over fluoxetine in the FST with more reductions of the immobility time. Compound 3g also reduced immobility time significantly in a tail suspension test (TST) at the dosage of 50 mg/kg, though its anti-immobility activity was inferior to that of fluoxetine. An open field test was carried out and it eliminated the false-positive possibility of 3g in the FST and TST, which complementarily supported the antidepressant activity of 3g. We also found that almost all compounds except 3k exhibited antiseizure activity in the maximal electroshock seizure (MES) model at 100 or 300 mg/kg. Compounds 3c, 3f, and 3g displayed the ED50 of 63.4, 78.9, and 84.9 mg/kg, and TD50 of 264.1, 253.5, and 439.9 mg/kg, respectively. ELISA assays proved that the mechanism for the antiseizure and antidepressant activities of compound 3g was via affecting the concentration of GABA in mice brain. The molecular docking study showed a good interaction between 3g and the amino acid residue of the GABAA receptor. Excellent drug-like properties and pharmacokinetic properties of compound 3al were also predicted by Discovery Studio. These findings provided a new skeleton to develop agents for the treatment of epilepsy and depression comorbidities. Full article
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28 pages, 4608 KiB  
Article
Surface Properties of Graffiti Coatings on Sensitive Surfaces Concerning Their Removal with Formulations Based on the Amino-Acid-Type Surfactants
Molecules 2023, 28(4), 1986; https://doi.org/10.3390/molecules28041986 - 20 Feb 2023
Cited by 2 | Viewed by 1690
Abstract
Water-in-oil (w/o) nanoemulsions stabilized with amino acid surfactants (AAS) are one example of nanotechnology detergents of the “brush on, wipe off”-type for removing graffiti coatings from different sensitive surfaces. The high-pressure homogenization (HPH) process was used to obtain the nanostructured fluids (NSFs), including [...] Read more.
Water-in-oil (w/o) nanoemulsions stabilized with amino acid surfactants (AAS) are one example of nanotechnology detergents of the “brush on, wipe off”-type for removing graffiti coatings from different sensitive surfaces. The high-pressure homogenization (HPH) process was used to obtain the nanostructured fluids (NSFs), including the non-toxic and eco-friendly components such as AAS, esterified vegetable oils, and ethyl lactate. The most effective NSF detergent was determined by response surface methodology (RSM) optimization. Afterwards, several surface properties, i.e., topography, wettability, surface free energy, and the work of water adhesion to surfaces before and after their coverage with the black graffiti paint, as well as after the removal of the paint layers by the eco-remover, were determined. It was found that the removal of graffiti with the use of the NSF detergent is more dependent on the energetic properties and microporous structure of the paint coatings than on the properties of the substrates on which the layers were deposited. The use of NSFs and knowledge of the surface properties could enable the development of versatile detergents that would remove unwanted contamination from various surfaces easily and in a controlled way. Full article
(This article belongs to the Special Issue Surfactants and Interfaces)
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17 pages, 21551 KiB  
Article
Elucidating Flavonoid and Antioxidant Activity in Edible and Medicinal Herbs Woodwardia japonica (L.f.) Sm. Based on HPLC-ESI-TOF-MS and Artificial Neural Network Model: Response to Climatic Factors
Molecules 2023, 28(4), 1985; https://doi.org/10.3390/molecules28041985 - 20 Feb 2023
Viewed by 1325
Abstract
Woodwardia japonica is a kind of great potential edible and medicinal fern. In a previous study, it was found that flavonoid and antioxidant activity of W. japonica from different sites were different. However, the cause of the differences has still been unclear, which [...] Read more.
Woodwardia japonica is a kind of great potential edible and medicinal fern. In a previous study, it was found that flavonoid and antioxidant activity of W. japonica from different sites were different. However, the cause of the differences has still been unclear, which has restricted the utilization of W. japonica. In this paper, flavonoid and antioxidant activity of W. japonica from nine different regions were determined with the method of a colorimetric assay with UV-VIS spectrophotometry and HPLC-ESI-TOF-MS, and the effects of climate factors on flavonoids and antioxidant activities were evaluated by mathematical modeling and statistical methods. The results showed: (1) total flavonoid content (TFC) of W. japonica from Wuyi Mountain (Jiangxi) was the highest, which might be related to the low temperature; (2) the differences of antioxidant activities of W. japonica might be related to precipitation; (3) five flavonols, two flavones and one isoflavone were tentatively identified in W. japonica; (4) flavonol and isoflavone might be affected by sunshine duration, and flavones were probably related to temperature. In conclusion, the effects of climate factors on flavonoids and antioxidants are significant, which would provide an important basis for further exploring the mechanism of climate affecting secondary metabolites. Full article
(This article belongs to the Special Issue Analyses and Applications of Phenolic Compounds in Food)
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15 pages, 2079 KiB  
Article
Integrating Siderophore Substructures in Thiol-Based Metallo-β-Lactamase Inhibitors
Molecules 2023, 28(4), 1984; https://doi.org/10.3390/molecules28041984 - 20 Feb 2023
Cited by 1 | Viewed by 1659
Abstract
Metallo beta lactamases (MBLs) are among the most problematic resistance mechanisms of multidrug-resistant Gram-negative pathogens due to their broad substrate spectrum and lack of approved inhibitors. In this study, we propose the integration of catechol substructures into the design of thiol-based MBL inhibitors, [...] Read more.
Metallo beta lactamases (MBLs) are among the most problematic resistance mechanisms of multidrug-resistant Gram-negative pathogens due to their broad substrate spectrum and lack of approved inhibitors. In this study, we propose the integration of catechol substructures into the design of thiol-based MBL inhibitors, aiming at mimicking bacterial siderophores for the active uptake by the iron acquisition system of bacteria. We synthesised two catechol-containing MBL inhibitors, as well as their dimethoxy counterparts, and tested them for in vitro inhibitory activity against NDM-1, VIM-1, and IMP-7. We demonstrated that the most potent catechol-containing MBL inhibitor is able to bind Fe3+ ions. Finally, we could show that this compound restores the antibiotic activity of imipenem in NDM-1-expressing K. pneumoniae, while leaving HUVEC cells completely unaffected. Thus, siderophore-containing MBL inhibitors might be a valuable strategy to overcome bacterial MBL-mediated resistance to beta lactam antibiotics. Full article
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23 pages, 3305 KiB  
Article
Multicomponent Domino Cyclization of Ethyl Trifluoropyruvate with Methyl Ketones and Amino Alcohols as A New Way to γ-Lactam Annulated Oxazacycles
Molecules 2023, 28(4), 1983; https://doi.org/10.3390/molecules28041983 - 20 Feb 2023
Viewed by 1187
Abstract
A new route to bicyclic γ-lactams was found, which was proposed as a three-component cyclization of ethyl trifluoropyruvate with methyl ketones and 1,2-, 1,3-amino alcohols. As a result, a series of trifluoromethyl-substituted tetrahydropyrrolo [2,1-b]oxazol-5-ones and tetrahydropyrrolo[2,1-b][1,3]oxazine-6-ones was synthesized, in [...] Read more.
A new route to bicyclic γ-lactams was found, which was proposed as a three-component cyclization of ethyl trifluoropyruvate with methyl ketones and 1,2-, 1,3-amino alcohols. As a result, a series of trifluoromethyl-substituted tetrahydropyrrolo [2,1-b]oxazol-5-ones and tetrahydropyrrolo[2,1-b][1,3]oxazine-6-ones was synthesized, in which the substituent at the nodal carbon atom was varied. The introduction of a twofold excess of ethyl trifluoropyruvate in reactions with amino alcohols and acetone made it possible to obtain the same bicycles, but functionalized with a hydroxyester fragment, which are formed due to four-component interactions of the reagents. Transformations with 2-butanone and aminoethanol lead predominantly to similar bicycles, while an analogous reaction with aminopropanol gives N-hydroxypropyl-2,3-dihydropyrrol-5-one. Almost all bicycles are formed as two diastereomers, the structure of which was determined using 1H, 19F, 13C NMR spectroscopy, including two-dimensional experiments and XRD analysis. A domino mechanism for the formation of tetrahydropyrrolo[2,1-b]oxazacycles was proposed, which was confirmed by their stepwise synthesis through the preliminary preparation of the aldol and bis-aldol from ethyl trifluoropyruvate and methyl ketones. Full article
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19 pages, 919 KiB  
Review
Research and Therapeutic Approaches in Stem Cell Genome Editing by CRISPR Toolkit
Molecules 2023, 28(4), 1982; https://doi.org/10.3390/molecules28041982 - 20 Feb 2023
Cited by 3 | Viewed by 3311
Abstract
The most widely used genome editing toolkit is CRISPR (clustered regularly interspaced short palindromic repeats). It provides the possibility of replacing and modifying DNA and RNA nucleotides. Furthermore, with advancements in biological technology, inhibition and activation of the transcription of specific gene(s) has [...] Read more.
The most widely used genome editing toolkit is CRISPR (clustered regularly interspaced short palindromic repeats). It provides the possibility of replacing and modifying DNA and RNA nucleotides. Furthermore, with advancements in biological technology, inhibition and activation of the transcription of specific gene(s) has become possible. Bioinformatics tools that target the evolution of CRISPR-associated protein 9 (Cas9) turn this protein into a vehicle that is specific for a DNA or RNA region with single guide RNA (sgRNA). This toolkit could be used by researchers to investigate the function of stem cell gene(s). Here, in this review article, we cover recent developments and applications of this technique in stem cells for research and clinical purposes and discuss different CRISPR/Cas technologies for knock-out, knock-in, activation, or inhibition of gene expression. Additionally, a comparison of several deliveries and off-target detecting strategies is discussed. Full article
(This article belongs to the Section Molecular Structure)
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30 pages, 4579 KiB  
Review
Quinones as Promising Compounds against Respiratory Viruses: A Review
Molecules 2023, 28(4), 1981; https://doi.org/10.3390/molecules28041981 - 20 Feb 2023
Cited by 2 | Viewed by 2458
Abstract
Respiratory viruses represent a world public health problem, giving rise to annual seasonal epidemics and several pandemics caused by some of these viruses, including the COVID-19 pandemic caused by the novel SARS-CoV-2, which continues to date. Some antiviral drugs have been licensed for [...] Read more.
Respiratory viruses represent a world public health problem, giving rise to annual seasonal epidemics and several pandemics caused by some of these viruses, including the COVID-19 pandemic caused by the novel SARS-CoV-2, which continues to date. Some antiviral drugs have been licensed for the treatment of influenza, but they cause side effects and lead to resistant viral strains. Likewise, aerosolized ribavirin is the only drug approved for the therapy of infections by the respiratory syncytial virus, but it possesses various limitations. On the other hand, no specific drugs are licensed to treat other viral respiratory diseases. In this sense, natural products and their derivatives have appeared as promising alternatives in searching for new compounds with antiviral activity. Besides their chemical properties, quinones have demonstrated interesting biological activities, including activity against respiratory viruses. This review summarizes the activity against respiratory viruses and their molecular targets by the different types of quinones (both natural and synthetic). Thus, the present work offers a general overview of the importance of quinones as an option for the future pharmacological treatment of viral respiratory infections, subject to additional studies that support their effectiveness and safety. Full article
(This article belongs to the Collection Featured Reviews in Natural Products Chemistry)
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20 pages, 4130 KiB  
Review
Advances on Hormones in Cosmetics: Illegal Addition Status, Sample Preparation, and Detection Technology
Molecules 2023, 28(4), 1980; https://doi.org/10.3390/molecules28041980 - 20 Feb 2023
Cited by 2 | Viewed by 2094
Abstract
Owing to the rapid development of the cosmetic industry, cosmetic safety has become the focus of consumers’ attention. However, in order to achieve the desired effects in the short term, the illegal addition of hormones in cosmetics has emerged frequently, which could induce [...] Read more.
Owing to the rapid development of the cosmetic industry, cosmetic safety has become the focus of consumers’ attention. However, in order to achieve the desired effects in the short term, the illegal addition of hormones in cosmetics has emerged frequently, which could induce skin problems and even skin cancer after long-term use. Therefore, it is of great significance to master the illegal addition in cosmetics and effectively detect the hormones that may exist in cosmetics. In this review, we analyze the illegally added hormone types, detection values, and cosmetic types, as well as discuss the hormone risks in cosmetics for human beings, according to the data in unqualified cosmetics in China from 2017 to 2022. Results showed that although the frequency of adding hormones in cosmetics has declined, hormones are still the main prohibited substances in illegal cosmetics, especially facial masks. Because of the complex composition and the low concentration of hormones in cosmetics, it is necessary to combine efficient sample preparation technology with instrumental analysis. In order to give the readers a comprehensive overview of hormone analytical technologies in cosmetics, we summarize the advanced sample preparation techniques and commonly used detection techniques of hormones in cosmetics in the last decade (2012–2022). We found that ultrasound-assisted extraction, solid phase extraction, and microextraction coupled with chromatographic analysis are still the most widely used analytical technologies for hormones in cosmetics. Through the investigation of market status, the summary of sample pretreatment and detection technologies, as well as the discussion of their development trends in the future, our purpose is to provide a reference for the supervision of illegal hormone residues in cosmetics. Full article
(This article belongs to the Special Issue Development of Sample Preparation and Analytical Methods)
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15 pages, 2690 KiB  
Article
68Ga-Labeled [Thz14]Bombesin(7–14) Analogs: Promising GRPR-Targeting Agonist PET Tracers with Low Pancreas Uptake
Molecules 2023, 28(4), 1977; https://doi.org/10.3390/molecules28041977 - 20 Feb 2023
Cited by 1 | Viewed by 1542
Abstract
With overexpression in various cancers, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer imaging and therapy. However, the high pancreas uptake of reported GRPR-targeting radioligands limits their clinical application. Our goal was to develop 68Ga-labeled agonist tracers for detecting [...] Read more.
With overexpression in various cancers, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer imaging and therapy. However, the high pancreas uptake of reported GRPR-targeting radioligands limits their clinical application. Our goal was to develop 68Ga-labeled agonist tracers for detecting GRPR-expressing tumors with positron emission tomography (PET), and compare them with the clinically validated agonist PET tracer, [68Ga]Ga-AMBA. Ga-TacBOMB2, TacBOMB3, and TacBOMB4, derived from [Thz14]Bombesin(7–14), were confirmed to be GRPR agonists by a calcium mobilization study, and their binding affinities (Ki(GRPR)) were determined to be 7.62 ± 0.19, 6.02 ± 0.59, and 590 ± 36.5 nM, respectively, via in vitro competition binding assays. [68Ga]Ga-TacBOMB2, [68Ga]Ga-TacBOMB3, and [68Ga]Ga-AMBA clearly visualized PC-3 tumor xenografts in a PET imaging study. [68Ga]Ga-TacBOMB2 showed comparable tumor uptake but superior tumor-to-background contrast ratios when compared to [68Ga]Ga-AMBA. Moreover, [68Ga]Ga-TacBOMB2 and [68Ga]Ga-TacBOMB3 showed a much lower rate of uptake in the pancreas (1.30 ± 0.14 and 2.41 ± 0.72%ID/g, respectively) than [68Ga]Ga-AMBA (62.4 ± 4.26%ID/g). In conclusion, replacing Met14 in the GRPR-targeting sequence with Thz14 retains high GRPR-binding affinity and agonist properties. With good tumor uptake and tumor-to-background uptake ratios, [68Ga]Ga-TacBOMB2 is promising for detecting GRPR-expressing tumors. The much lower pancreas uptake of [68Ga]Ga-TacBOMB2 and [68Ga]Ga-TacBOMB3 suggests that [Thz14]Bombesin(7–14) is a promising targeting vector for the design of GRPR-targeting radiopharmaceuticals, especially for radioligand therapy application. Full article
(This article belongs to the Special Issue Design, Synthesis and Evaluation of Theranostic Radiopharmaceuticals)
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12 pages, 5717 KiB  
Article
Lactose and Galactose Promote the Crystallization of Human Galectin-10
Molecules 2023, 28(4), 1979; https://doi.org/10.3390/molecules28041979 - 19 Feb 2023
Viewed by 1770
Abstract
Galectin-10 (Gal-10) forms Charcot–Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer–dimer equilibrium [...] Read more.
Galectin-10 (Gal-10) forms Charcot–Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer–dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases. Full article
(This article belongs to the Special Issue Recent Opinion on Protein-Carbohydrate Interactions)
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13 pages, 5549 KiB  
Article
Reversible Luminescent Switching Induced by Heat/Water Treatment in a Zero-Dimensional Hybrid Antimony(Ⅲ) Chloride
Molecules 2023, 28(4), 1978; https://doi.org/10.3390/molecules28041978 - 19 Feb 2023
Cited by 6 | Viewed by 1812
Abstract
Recently zero-dimensional (0-D) inorganic–organic metal halides (IOMHs) have become a promising class of optoelectronic materials. Herein, we report a new photoluminescent (PL) 0-D antimony(III)-based IOMH single crystal, namely [H2BPZ][SbCl5]·H2O (BPZ = benzylpiperazine). Photophysical characterizations indicate that [H [...] Read more.
Recently zero-dimensional (0-D) inorganic–organic metal halides (IOMHs) have become a promising class of optoelectronic materials. Herein, we report a new photoluminescent (PL) 0-D antimony(III)-based IOMH single crystal, namely [H2BPZ][SbCl5]·H2O (BPZ = benzylpiperazine). Photophysical characterizations indicate that [H2BPZ][SbCl5]·H2O exhibits singlet/triplet dual-band emission. Density functional theory (DFT) calculations suggest that [H2BPZ][SbCl5]·H2O has the large energy difference between singlet and triplet states, which might induce the dual emission in this compound. Temperature-dependent PL spectra analyses suggest the soft lattice and strong electron–phonon coupling in this compound. Thermogravimetric analysis shows that the water molecules in the lattice of the title crystal could be removed by thermal treatment, giving rise to a dehydrated phase of [H2BPZ][SbCl5]. Interestingly, such structural transformation is accompanied by a reversible PL emission transition between red light (630 nm, dehydrated phase) and yellow light (595 nm, water-containing phase). When being exposed to an environment with 77% relative humidity, the emission color of the dehydrated phase was able to change from red to yellow within 20 s, and the red emission could be restored after reheating. The red to yellow emission switching could be achieved in acetone with water concentration as low as 0.2 vol%. The reversible PL transition phenomenon makes [H2BPZ][SbCl5]·H2O a potential material for luminescent water-sensing. Full article
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17 pages, 3426 KiB  
Article
Influence of Mutations of Conserved Arginines on Neuropeptide Binding in the DPP III Active Site
Molecules 2023, 28(4), 1976; https://doi.org/10.3390/molecules28041976 - 19 Feb 2023
Viewed by 1327
Abstract
Dipeptidyl peptidase III (DPP III), a zinc exopeptidase, is involved in the final steps of intercellular protein degradation and has a marked affinity for opioid peptides such as enkephalins and endomorphins. Recently, we characterized a number of neuropeptides as potential substrates and inhibitors [...] Read more.
Dipeptidyl peptidase III (DPP III), a zinc exopeptidase, is involved in the final steps of intercellular protein degradation and has a marked affinity for opioid peptides such as enkephalins and endomorphins. Recently, we characterized a number of neuropeptides as potential substrates and inhibitors of human DPP III and provided an explanation for their differential behavior. These studies prompted us to investigate the influence of the conserved R399 and R669 on neuropeptides binding to DPP III. Measuring kinetic parameters in inhibitory assays, we found that mutation of R669 to Ala or Met significantly reduced the inhibitory properties of the slow substrates tynorphin and valorphin, whereas the effects on binding of the good substrates Arg2-2NA and Leu-enkephalin were small. Molecular dynamics simulations of wild-type (WT) and mutant DPP III complexes with Leu-enkephalin, tynorphin, valorphin, and Arg2-2NA in conjunction with calculations of binding free energies revealed that the lower inhibitory potency of slow substrates in the R669A mutant can be explained by the lower binding affinity of tynorphin and the higher propensity of valorphin to hydrolyze in the mutant than in WT. The R399A mutation was shown to affect the binding and/or hydrolysis of both good and slow substrates, with the effects on Leu-enkephalin being the most pronounced. Full article
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15 pages, 1598 KiB  
Article
Variation of Aroma Components of Pasteurized Yogurt with Different Process Combination before and after Aging by DHS/GC-O-MS
Molecules 2023, 28(4), 1975; https://doi.org/10.3390/molecules28041975 - 19 Feb 2023
Cited by 1 | Viewed by 1663
Abstract
Pasteurized yogurt is a healthy yogurt that can be stored in ambient temperature conditions. Dynamic headspace sampling (DHS) combined with gas chromatography-olfactory mass spectrometry (GC-O-MS), sensory evaluation, electronic nose (E-nose), and partial least squares discriminant analysis (PLS-DA) were used to analyze the flavor [...] Read more.
Pasteurized yogurt is a healthy yogurt that can be stored in ambient temperature conditions. Dynamic headspace sampling (DHS) combined with gas chromatography-olfactory mass spectrometry (GC-O-MS), sensory evaluation, electronic nose (E-nose), and partial least squares discriminant analysis (PLS-DA) were used to analyze the flavor changes of pasteurized yogurt with different process combinations before and after aging. The results of odor profiles showed that the sensory descriptors of fermented, sweet, and sour were greatly affected by different process combinations. The results of odor-active compounds and relative odor activity value (r-OAV) showed that the combination of the production process affected the overall odor profile of pasteurized yogurt, which was consistent with the sensory evaluation results. A total of 15 odor-active compounds of 38 volatile compounds were detected in pasteurized yogurt samples. r-OAV results revealed that hexanal, (E)-2-octenal, 2-heptanone, and butanoic acid may be important odor-active compounds responsible for off-odor in aged, pasteurized yogurt samples. PLS-DA and variable importance of projection (VIP) results showed that butanoic acid, hexanal, acetoin, decanoic acid, 1-pentanol, 1-nonanal, and hexanoic acid were differential compounds that distinguish pasteurized yogurt before and after aging. Full article
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13 pages, 3314 KiB  
Article
Cinnamomum japonicum Siebold Branch Extracts Attenuate NO and ROS Production via the Inhibition of p38 and JNK Phosphorylation
Molecules 2023, 28(4), 1974; https://doi.org/10.3390/molecules28041974 - 19 Feb 2023
Cited by 1 | Viewed by 1277
Abstract
Cinnamomum japonicum (CJ) is widely distributed in Asian countries like Korea, China, and Japan. Modern pharmacological studies have demonstrated that it exhibits various biological activities, including antioxidant and anti-inflammatory effects. However, most studies have confirmed the efficacy of its water extract but not [...] Read more.
Cinnamomum japonicum (CJ) is widely distributed in Asian countries like Korea, China, and Japan. Modern pharmacological studies have demonstrated that it exhibits various biological activities, including antioxidant and anti-inflammatory effects. However, most studies have confirmed the efficacy of its water extract but not that of its other extracts. Therefore, in this study, Cinnamomum japonicum Siebold branches (CJB: 70% EtOH extract) were separated using hexane, chloroform, ethyl acetate (CJB3), butanol, and water. Then, their antioxidative activities and phenolic contents were measured. Results revealed that the antioxidant activities and phenolic contents of CJB3 were higher than those of the other extracts. Further, the inhibitory and anti-inflammatory effect of CJB3 on lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and LPS-activated macrophages, respectively, was determined. CJB3 suppressed oxidative stress in LPS-activated cells and dose-dependently decreased LPS-stimulated ROS production. CJB3 reduced oxidative stress and reversed the glutathione decrease in LPS-activated RAW264.7 cells. The inhibitory and reducing effect of CJB3 on LPS-induced nitric oxide (NO) production and inducible NO synthase protein and messenger RNA levels, respectively, was investigated. CJB3 inhibited LPS-induced cytokine production and p38 and c-Jun N-terminal kinase (JNK) phosphorylation but not extracellular signal-regulated kinase phosphorylation. Overall, the study results suggest that CJB3 may exert its anti-inflammatory effects via the suppression of p38, JNK, and c-Jun activation. Full article
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35 pages, 5802 KiB  
Review
The Impact of Fluorination on the Design of Histone Deacetylase Inhibitors
Molecules 2023, 28(4), 1973; https://doi.org/10.3390/molecules28041973 - 19 Feb 2023
Cited by 4 | Viewed by 2374
Abstract
In recent years, histone deacetylases (HDACs) have emerged as promising targets in the treatment of cancer. The approach is to inhibit HDACs with drugs known as HDAC inhibitors (HDACis). Such HDACis are broadly classified according to their chemical structure, e.g., hydroxamic acids, benzamides, [...] Read more.
In recent years, histone deacetylases (HDACs) have emerged as promising targets in the treatment of cancer. The approach is to inhibit HDACs with drugs known as HDAC inhibitors (HDACis). Such HDACis are broadly classified according to their chemical structure, e.g., hydroxamic acids, benzamides, thiols, short-chain fatty acids, and cyclic peptides. Fluorination plays an important role in the medicinal–chemical design of new active representatives. As a result of the introduction of fluorine into the chemical structure, parameters such as potency or selectivity towards isoforms of HDACs can be increased. However, the impact of fluorination cannot always be clearly deduced. Nevertheless, a change in lipophilicity and, hence, solubility, as well as permeability, can influence the potency. The selectivity towards certain HDACs isoforms can be explained by special interactions of fluorinated compounds with the structure of the slightly different enzymes. Another aspect is that for a more detailed investigation of newly synthesized fluorine-containing active compounds, fluorination is often used for the purpose of labeling. Aside from the isotope 19F, which can be detected by nuclear magnetic resonance spectroscopy, the positron emission tomography of 18F plays a major role. However, to our best knowledge, a survey of the general effects of fluorination on HDACis development is lacking in the literature to date. Therefore, the aim of this review is to highlight the introduction of fluorine in the course of chemical synthesis and the impact on biological activity, using selected examples of recently developed fluorinated HDACis. Full article
(This article belongs to the Special Issue Bioorganic Chemistry: Current and Future Perspectives)
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10 pages, 1830 KiB  
Article
Anti-Cancer Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) and Its Cellular Mechanisms against Human Hepatoma Cells
Molecules 2023, 28(4), 1972; https://doi.org/10.3390/molecules28041972 - 19 Feb 2023
Cited by 3 | Viewed by 2336
Abstract
Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer that occurs in hepatocytes. Although many chemical drugs, e.g., cisplatin, methotrexate, taxis, and doxorubicin are used to treat HCC, there have been numerous reports related to the side effects of these [...] Read more.
Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer that occurs in hepatocytes. Although many chemical drugs, e.g., cisplatin, methotrexate, taxis, and doxorubicin are used to treat HCC, there have been numerous reports related to the side effects of these drugs (e.g., emerging drug resistance, bone marrow failure, and gastrointestinal disorders). These issues led scientists to search for the novel anti-cancer drugs, mainly in natural products with greater efficiency and less toxicity. The current survey was intended to assess the anti-cancer effects of queen bee acid (10-Hydroxy-2-Decenoic Acid, 10-HDA) and its cellular mechanisms against the human hepatoma cell line HepG2. Materials and Methods: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to evaluate the effect of 10-HDA on the viability of HepG2 cells. The initial and late apoptosis in the HepG2 cells treated with 10-HDA were assessed by the Annexin-V (AV) assay. The level of the gene and protein expression of some apoptosis genes (e.g., caspase-3, Bcl-2-associated X protein (BAX), and B-cell lymphoma protein 2 (Bcl-2)), Poly (ADP-ribose) polymerases (PARP), and miRNA-34a (miR-34a), were measured by real-time PCR and Western blot. Results: The obtained findings revealed that HepG2 cell viability was markedly reduced (p < 0.01) following exposure to 10-HDA in a dose-dependent matter. The calculated half maximal cytotoxic concentration (CC50) value of 10-HDA was 59.6 µg/mL for HepG2 cells, while this value for normal THLE-3 cells was 106.4 µg/mL. We found that 10-HDA markedly elevated (p < 0.01) the percentage of necrotic and apoptotic cells from 0.94 to 9.7 and 27.6%, respectively. The real-time PCR results showed that the expression levels of the caspase-3, Bax, and miR-34a genes were significantly (p < 0.001) elevated. Contrary to these results, a significant (p < 0.01) reduction in the expression level of the Bcl2 gene was observed. The levels of protein expression of Caspase-3, PARP, and Bax were markedly elevated following exposure of HepG2 cells to 10-HDA at ¼ CC50, ½ CC50, and CC50. The level of protein expression of Bcl-2 was markedly reduced following exposure of HepG2 cells to 10-HDA at ¼ CC50, ½ CC50, and CC50 (p < 0.01). Conclusion: The current results confirmed the potent in vitro cytotoxic effects of 10-HDA on HepG2 cells with no significant cytotoxic effects on normal cells. Although its mechanisms of action have not been fully studied, the induction of apoptosis via different pathways was determined as one of the principle mechanisms of action of 10-HDA against HepG2 cells. Nevertheless, additional surveys must be performed to clearly understand the mechanisms of action and safety of this fatty acid. Full article
(This article belongs to the Special Issue Recent Advances in Anticancer Drugs III)
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16 pages, 2949 KiB  
Article
A Natural Glucan from Black Bean Inhibits Cancer Cell Proliferation via PI3K-Akt and MAPK Pathway
Molecules 2023, 28(4), 1971; https://doi.org/10.3390/molecules28041971 - 19 Feb 2023
Cited by 3 | Viewed by 1342
Abstract
A natural α-1,6-glucan named BBWPW was identified from black beans. Cell viability assay showed that BBWPW inhibited the proliferation of different cancer cells, especially HeLa cells. Flow cytometry analysis indicated that BBWPW suppressed the HeLa cell cycle in the G2/M phase. Consistently, RT-PCR [...] Read more.
A natural α-1,6-glucan named BBWPW was identified from black beans. Cell viability assay showed that BBWPW inhibited the proliferation of different cancer cells, especially HeLa cells. Flow cytometry analysis indicated that BBWPW suppressed the HeLa cell cycle in the G2/M phase. Consistently, RT-PCR experiments displayed that BBWPW significantly impacts the expression of four marker genes related to the G2/M phase, including p21, CDK1, Cyclin B1, and Survivin. To explore the molecular mechanism of BBWPW to induce cell cycle arrest, a transcriptome-based target inference approach was utilized to predict the potential upstream pathways of BBWPW and it was found that the PI3K-Akt and MAPK signal pathways had the potential to mediate the effects of BBWPW on the cell cycle. Further experimental tests confirmed that BBWPW increased the expression of BAD and AKT and decreased the expression of mTOR and MKK3. These results suggested that BBWPW could regulate the PI3K-Akt and MAPK pathways to induce cell cycle arrest and ultimately inhibit the proliferation of HeLa cells, providing the potential of the black bean glucan to be a natural anticancer drug. Full article
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