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Molecules, Volume 24, Issue 12 (June-2 2019) – 152 articles

Cover Story (view full-size image): Anion–π interactions are controversial supramolecular forces whose full recognition has encountered some resistance within the scientific community. Their existence has long been questioned not only in solution, but also in the solid state. Moreover, anion–π forces are oftentimes set aside for applications due to their scarcely manifest directional character.
The class of homologous s-tetrazine-based receptors L1–L4 successfully demonstrates predictability and directionality of anion–π interactions in the solid state. Moreover, owing to the quadrupole moment of the s-tetrazine and to the solvent effect arising from the peculiar solvation of the L1–L4 ligands in water, anion–π interactions can be made sufficiently strong that they also remain the preferred type of interactions in aqueous solution. View this paper.
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12 pages, 7155 KiB  
Article
High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
by Vivien Kauschke, Felix Maximilian Hessland, David Vehlow, Martin Müller, Christian Heiss and Katrin Susanne Lips
Molecules 2019, 24(12), 2346; https://doi.org/10.3390/molecules24122346 - 25 Jun 2019
Cited by 7 | Viewed by 3432
Abstract
Fracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implant materials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles [...] Read more.
Fracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implant materials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles can serve as drug delivery systems for growth factors like Brain-Derived Neurotrophic Factor (BDNF), which stimulated osteoblast differentiation. Therefore, polyelectrolyte complex nanoparticles (PEC-NPs) consisting of poly(l-lysine) (PLL) and cellulose sulfate (CS), with or without addition of BDNF, were used to analyze their effect on osteoclasts in vitro. Live cell images showed that osteoclast numbers decreased after application of high PLL/CS PEC-NPs concentrations independent of whether BDNF was added or not. Real-time RT-PCR revealed that relative mRNA expression of cathepsin K and calcitonin receptor significantly declined after incubation of osteoclasts with high concentrations of PLL/CS PEC-NPs. Furthermore, Enzyme-Linked Immunosorbent Assay indicated that tartrate-resistant acidic phosphatase 5b activity was significantly reduced in the presence of high PLL/CS PEC-NPs concentrations. Consistent with these results, the pit formation analysis showed that less hydroxyapatite was resorbed by osteoclasts after incubation with high concentrations of PLL/CS PEC-NPs. BDNF had no influence on osteoclasts. We conclude that highly concentrated PLL/CS PEC-NPs dosages decreased osteoclastogenesis and osteoclasts activity. Moreover, BDNF might be a promising growth factor for osteoporotic fracture treatment since it did not increase osteoclast activity. Full article
(This article belongs to the Special Issue Inorganic Nanomaterials)
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20 pages, 5628 KiB  
Article
Exploring Nanosilver-Coated Hollow Fiber Microfiltration to Mitigate Biofouling for High Loading Membrane Bioreactor
by Huy Quang Le, Alieu Sowe, Shiao-Shing Chen, Chinh Cong Duong, Saikat Sinha Ray, Thanh Ngoc-Dan Cao and Nguyen Cong Nguyen
Molecules 2019, 24(12), 2345; https://doi.org/10.3390/molecules24122345 - 25 Jun 2019
Cited by 5 | Viewed by 2980
Abstract
For the first time, a nanosilver-coated hollow fiber microfiltration (MF) was fabricated by a simple chemical reduction method, then tested for membrane biofouling mitigation study under extreme high mixed liquor suspended solid (MLSS) concentration for long term. This study presents a simple and [...] Read more.
For the first time, a nanosilver-coated hollow fiber microfiltration (MF) was fabricated by a simple chemical reduction method, then tested for membrane biofouling mitigation study under extreme high mixed liquor suspended solid (MLSS) concentration for long term. This study presents a simple and novel technique to modify a commercially available MF membrane using silver nanoparticles (AgNPs) followed by an investigation of mitigating membrane biofouling potentials using this modified membrane to compare with an unmodified membrane for 60-day operation period. The modified membranes showed that AgNPs was attached to the MF-membrane successfully with a high density of 119.85 ± 5.42 mg/m2. After long-term testing of 60 days in membrane bioreactor with a MLSS concentration of 11,000 mg/L, specific flux of the AgNPs coated MF (AgNPs-MF) decreased 59.7%, while the specific flux of the unmodified membrane dropped 81.8%, resulted from the increase of transmembrane vacuum pressure for the AgNPs-MF was lower than that of the unmodified one. The resistance-in-series model was used to calculate the resistance coefficients of membrane modules, and the result showed that the cake layer resistance coefficient of the unmodified membrane was 2.7 times higher than that of the AgNPs-MF after the 60-day operation, confirming that AgNPs displayed great antimicrobial properties to mitigate membrane biofouling under such high MLSS. Full article
(This article belongs to the Special Issue Sustainability in Membrane Production and Membrane Operations)
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15 pages, 4290 KiB  
Article
Essential Oil of Mentha aquatica var. Kenting Water Mint Suppresses Two-Stage Skin Carcinogenesis Accelerated by BRAF Inhibitor Vemurafenib
by Chih-Ting Chang, Wen-Ni Soo, Yu-Hsin Chen and Lie-Fen Shyur
Molecules 2019, 24(12), 2344; https://doi.org/10.3390/molecules24122344 - 25 Jun 2019
Cited by 9 | Viewed by 4587
Abstract
The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma; however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent HRASQ61L mutation. In a [...] Read more.
The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma; however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent HRASQ61L mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of Mentha aquatica var. Kenting Water Mint essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing HRASQ61L mutation, and its effect on inhibiting papilloma formation in a two-stage skin carcinogenesis mouse model with or without PLX4032 co-treatment. Our results revealed that KWM-EO effectively attenuated cell viability, colony formation, and the invasive and migratory abilities of PDV cells. Induction of G2/M cell-cycle arrest and apoptosis in PDV cells was also observed. KWM-EO treatment significantly decreased the formation of cutaneous papilloma further induced by PLX4032 in DT mice (DTP). Immunohistochemistry analyses showed overexpression of keratin14 and COX-2 in DT and DTP skin were profoundly suppressed by KWM-EO treatment. This study demonstrates that KWM-EO has chemopreventive effects against PLX4032-induced cutaneous side-effects in a DMBA/TPA-induced two-stage carcinogenesis model and will be worth further exploration for possible application in melanoma patients. Full article
(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)
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13 pages, 4449 KiB  
Article
Duodenoscope-Associated Infections beyond the Elevator Channel: Alternative Causes for Difficult Reprocessing
by Gheorghe G. Balan, Irina Rosca, Elena-Laura Ursu, Adrian Fifere, Cristian-Dragos Varganici, Florica Doroftei, Ioana-Andreea Turin-Moleavin, Vasile Sandru, Gabriel Constantinescu, Daniel Timofte, Gabriela Stefanescu, Anca Trifan and Catalin Victor Sfarti
Molecules 2019, 24(12), 2343; https://doi.org/10.3390/molecules24122343 - 25 Jun 2019
Cited by 16 | Viewed by 4744
Abstract
Objectives: Duodenoscopes have been widely used for both diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, but recently, numerous outbreaks of multidrug-resistant organisms (MDRO) infections have been reported which has led to extensive research for their possible causes. Consequently, the aim of this [...] Read more.
Objectives: Duodenoscopes have been widely used for both diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, but recently, numerous outbreaks of multidrug-resistant organisms (MDRO) infections have been reported which has led to extensive research for their possible causes. Consequently, the aim of this study is to search for possible duodenoscope surface damages that could provide an alternative and plausible source of infections. Materials and Methods: In order to assess both outer and inner surfaces, a duodenoscope was dismantled and samples were taken from the outer resin polymer and from the air/water, elevator, and working (biopsy) channels that were characterized by FTIR, DSC, TGA, AFM, SEM techniques and the antimicrobial activity were tested. Results: Alterations were noticed on both the coating and working channel polymers, with external alterations increasing progressively from the proximal sample to the distal sample near the tip of the scope. However, the results showed that the coating surface was still efficient against bacterial adhesion. Changes in surface texture and also morphological changes were shown. Conclusions: The study describes the impact of routine procedural use and reprocessing cycles on the duodenoscope, showing that these may possibly make it susceptible to bacterial contamination and MDRO biofilm formation due to difficult reprocessing of the altered surfaces. Full article
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20 pages, 4068 KiB  
Article
Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on α-Amylase and α-Glucosidase
by Mezna Saleh Altowyan, Assem Barakat, Abdullah Mohammed Al-Majid and H.A. Al-Ghulikah
Molecules 2019, 24(12), 2342; https://doi.org/10.3390/molecules24122342 - 25 Jun 2019
Cited by 27 | Viewed by 4187
Abstract
Inhibition of α-amylase and α-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar [...] Read more.
Inhibition of α-amylase and α-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[b]furan scaffold (compounds 2a–f), with a substituted isatin (compounds 3a–c) and heterocyclic amino acids (compounds 4a,b). The target spiroindolone analogues 5a–r were evaluated for their potential inhibitory activities against the enzymes α-amylase and α-glucosidase. Preliminary results indicated that some of the target compounds exhibit promising α-amylase and α-glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct 5r was found to be the most active (IC50 = 22.61 ± 0.54 μM and 14.05 ± 1.03 μM) as α-amylase and α-glucosidase inhibitors, with selectivity indexes of 0.62 and 1.60, respectively. Docking studies were carried out to confirm the binding interaction between the enzyme active site and the spiroindolone analogues. Full article
(This article belongs to the Special Issue Indole Derivatives: Synthesis and Application)
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14 pages, 2168 KiB  
Review
Methods to Discover and Evaluate Proteasome Small Molecule Stimulators
by Rachel A. Coleman and Darci J. Trader
Molecules 2019, 24(12), 2341; https://doi.org/10.3390/molecules24122341 - 25 Jun 2019
Cited by 15 | Viewed by 6066
Abstract
Protein accumulation has been identified as a characteristic of many degenerative conditions, such as neurodegenerative diseases and aging. In most cases, these conditions also present with diminished protein degradation. The ubiquitin-proteasome system (UPS) is responsible for the degradation of the majority of proteins [...] Read more.
Protein accumulation has been identified as a characteristic of many degenerative conditions, such as neurodegenerative diseases and aging. In most cases, these conditions also present with diminished protein degradation. The ubiquitin-proteasome system (UPS) is responsible for the degradation of the majority of proteins in cells; however, the activity of the proteasome is reduced in these disease states, contributing to the accumulation of toxic protein. It has been hypothesized that proteasome activity, both ubiquitin-dependent and -independent, can be chemically stimulated to reduce the load of protein in diseased cells. Several methods exist to identify and characterize stimulators of proteasome activity. In this review, we detail the ways in which protease activity can be enhanced and analyze the biochemical and cellular methods of identifying stimulators of both the ubiquitin-dependent and -independent proteasome activities. Full article
(This article belongs to the Special Issue Proteasome Regulators: Activators and Inhibitors)
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14 pages, 1660 KiB  
Article
Structural, Physical, and Antifungal Characterization of Starch Edible Films Added with Nanocomposites and Mexican Oregano (Lippia berlandieri Schauer) Essential Oil
by Rocio Aguilar-Sánchez, Ricardo Munguía-Pérez, Fatima Reyes-Jurado, Addí Rhode Navarro-Cruz, Teresa Soledad Cid-Pérez, Paola Hernández-Carranza, Silvia del Carmen Beristain-Bauza, Carlos Enrique Ochoa-Velasco and Raúl Avila-Sosa
Molecules 2019, 24(12), 2340; https://doi.org/10.3390/molecules24122340 - 25 Jun 2019
Cited by 22 | Viewed by 4107
Abstract
The aim of this study was to evaluate the structural, physical, and antifungal characteristics of starch edible films added with nanocomposites and Mexican oregano (Lippia berlandieri Schauer) essential oil (EO). Starch edible films were formulated with Mexican oregano EO (0%, 1%, or [...] Read more.
The aim of this study was to evaluate the structural, physical, and antifungal characteristics of starch edible films added with nanocomposites and Mexican oregano (Lippia berlandieri Schauer) essential oil (EO). Starch edible films were formulated with Mexican oregano EO (0%, 1%, or 2% v/v) and bentonite or halloysite (2%). Physical properties such as L* (luminosity), hue, film thickness, and O2 and CO2 permeability were determined. Structural analysis was carried out via atomic force microscopy (AFM). Antifungal activity against Aspergillus niger, Fusarium spp., and Rhizopus spp. was evaluated. The addition of EO and nanocomposites reduced luminosity, providing color to the edible films. Film thickness increased through the addition of EO concentration. O2 and CO2 permeability was increased by bentonite/EO films, and for halloysite films, CO2 permeability decreased as EO concentration increased. The addition of EO with both nanocomposites shows an evident morphological change in film structure, decreasing pore density and increasing pore size. In general, Mexican oregano EO added to edible starch films has an adequate fungicidal effect. The most sensitive microorganism tested was A. niger. Edible films added with Mexican oregano EO and nanocomposites show better physical and antifungal properties due to an adequate structural change in the biopolymer matrix. Full article
(This article belongs to the Special Issue Starch in Food Products)
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9 pages, 1389 KiB  
Article
Identification of Two New Phenanthrenes from Dendrobii Herba and Their Cytotoxicity towards Human Hypopharynx Squamous Carcinoma Cell (FaDu)
by Bomi Nam, Seung Mok Ryu, Dongho Lee, Chan-Hun Jung, Chang Hyun Jin, Jin-Baek Kim, Ik-Soo Lee and Ah-Reum Han
Molecules 2019, 24(12), 2339; https://doi.org/10.3390/molecules24122339 - 25 Jun 2019
Cited by 12 | Viewed by 3716
Abstract
Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3–9), two bibenzyls (10– [...] Read more.
Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3–9), two bibenzyls (10–12), and a lignan (13). Structures of 1 and 2 were elucidated by analyzing one-dimensional (1D) and two-dimensional (2D)-NMR and High-resolution electrospray ionization mass spectra (HR-ESI-MS) data. The absolute configuration of compound 1 was confirmed by the circular dichroism (CD) spectroscopic method. In cytotoxicity assay using FaDu human hypopharynx squamous carcinoma cell line, compounds 3–6, 8, 10, and 12 showed activities, with IC50 values that ranged from 2.55 to 17.70 μM. Full article
(This article belongs to the Section Natural Products Chemistry)
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15 pages, 3825 KiB  
Article
Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
by Di Chen, Yangmin Ma, Peiqi Li, Meng Liu, Yuan Fang, Jiejie Zhang, Bilin Zhang, Yuyu Hui and Yue Yin
Molecules 2019, 24(12), 2338; https://doi.org/10.3390/molecules24122338 - 25 Jun 2019
Cited by 39 | Viewed by 4575
Abstract
Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects [...] Read more.
Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC. Full article
(This article belongs to the Section Chemical Biology)
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17 pages, 4248 KiB  
Article
Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates
by J. Daniel Martínez, Pablo Valverde, Sandra Delgado, Cecilia Romanò, Bruno Linclau, Niels C. Reichardt, Stefan Oscarson, Ana Ardá, Jesús Jiménez-Barbero and F. Javier Cañada
Molecules 2019, 24(12), 2337; https://doi.org/10.3390/molecules24122337 - 25 Jun 2019
Cited by 38 | Viewed by 5948
Abstract
A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved [...] Read more.
A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The strategy employed allows not only screening of a mixture of compounds, but also obtaining valuable information on the specific sugar–protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc, and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, is also detected for the first time. The combination of the 19F with standard proton saturation transfer difference (1H-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture. Full article
(This article belongs to the Special Issue Carbohydrates in Synthesis)
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16 pages, 2792 KiB  
Review
Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication
by Simon Remy and Marc Litaudon
Molecules 2019, 24(12), 2336; https://doi.org/10.3390/molecules24122336 - 25 Jun 2019
Cited by 23 | Viewed by 4783
Abstract
Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the [...] Read more.
Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the cytopathic effect induced by the chikungunya virus. This review; which covers the years 2011 to 2019; lists all macrocyclic diterpenoids that have been evaluated for their ability to inhibit viral replication. The structure–activity relationships and the probable involvement of protein kinase C in their mechanism of action are also detailed. Full article
(This article belongs to the Special Issue Antimicrobial Properties of Natural Products)
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10 pages, 2020 KiB  
Article
An Isoxazole Derivative SHU00238 Suppresses Colorectal Cancer Growth through miRNAs Regulation
by Haoyu Wang, Yurui Ma, Yifan Lin, Jiajie Liu, Rui Chen, Bin Xu and Yajun Liang
Molecules 2019, 24(12), 2335; https://doi.org/10.3390/molecules24122335 - 25 Jun 2019
Cited by 14 | Viewed by 3397
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an [...] Read more.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an efficient method. In this study, we evaluated their effects on tumor cell growth. HCT116 cells were treated with isoxazole derivatives; an cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 (half maximal inhibitory concentration) of each derivative. Compound SHU00238, which was obtained by the copper nitrate-mediated [2+2+1] cycloaddition reaction of olefinic azlactone with naphthalene-1,4-dione, has a lower IC50; we analyzed its inhibitory activity in further assays. Cell apoptosis was estimated by flow cytometry analysis in vitro. SHU00238 injection was used to treat tumor-bearing mice. We found that SHU00238 suppressed cell viability and promoted cell apoptosis in vitro. SHU00238 treatment significantly inhibited colonic tumor growth in vivo. Furthermore, we compared the miRNAs expression changes in HCT116 cells before and after SHU00238 treatment. MiRNA profiling revealed that SHU00238 treatment affected cell fate by regulating a set of miRNAs. In conclusion, SHU00238 impedes CRC tumor cell proliferation and promotes cell apoptosis by miRNAs regulation. Full article
(This article belongs to the Special Issue Anti-Cancer Drug: Discovery, Development and Combination)
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19 pages, 6393 KiB  
Article
Modeling of Solid–Liquid Equilibria in Deep Eutectic Solvents: A Parameter Study
by Ahmad Alhadid, Liudmila Mokrushina and Mirjana Minceva
Molecules 2019, 24(12), 2334; https://doi.org/10.3390/molecules24122334 - 25 Jun 2019
Cited by 44 | Viewed by 4925
Abstract
Deep eutectic solvents (DESs) are potential alternatives to many conventional solvents in process applications. Knowledge and understanding of solid–liquid equilibria (SLE) are essential to characterize, design, and select a DES for a specific application. The present study highlights the main aspects that should [...] Read more.
Deep eutectic solvents (DESs) are potential alternatives to many conventional solvents in process applications. Knowledge and understanding of solid–liquid equilibria (SLE) are essential to characterize, design, and select a DES for a specific application. The present study highlights the main aspects that should be taken into account to yield better modeling, prediction, and understanding of SLE in DESs. The work is a comprehensive study of the parameters required for thermodynamic modeling of SLE—i.e., the melting properties of pure DES constituents and their activity coefficients in the liquid phase. The study is carried out for a hypothetical binary mixture as well as for selected real DESs. It was found that the deepest eutectic temperature is possible for components with low melting enthalpies and strong negative deviations from ideality in the liquid phase. In fact, changing the melting enthalpy value of a component means a change in the difference between solid and liquid reference state chemical potentials which results in different values of activity coefficients, leading to different interpretations and even misinterpretations of interactions in the liquid phase. Therefore, along with reliable modeling of liquid phase non-ideality in DESs, accurate estimation of the melting properties of their pure constituents is of clear significance in understanding their SLE behavior and for designing new DES systems. Full article
(This article belongs to the Special Issue Deep Eutectic Solvents)
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15 pages, 2613 KiB  
Article
Development of a Method for the Quantification of Clotrimazole and Itraconazole and Study of Their Stability in a New Microemulsion for the Treatment of Sporotrichosis
by Patricia Garcia Ferreira, Carolina Guimarães de Souza Lima, Letícia Lorena Noronha, Marcela Cristina de Moraes, Fernando de Carvalho da Silva, Alessandra Lifsitch Viçosa, Débora Omena Futuro and Vitor Francisco Ferreira
Molecules 2019, 24(12), 2333; https://doi.org/10.3390/molecules24122333 - 25 Jun 2019
Cited by 15 | Viewed by 5126
Abstract
Sporotrichosis occurs worldwide and is caused by the fungus Sporothrix brasiliensis. This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be [...] Read more.
Sporotrichosis occurs worldwide and is caused by the fungus Sporothrix brasiliensis. This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be effective against S. brasiliensis yeasts. This association was formulated as a microemulsion containing benzyl alcohol as oil, Tween® 60 and propylene glycol as surfactant and cosurfactant, respectively, and water. Initially, the compatibility between clotrimazole and itraconazole was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (PXRD). Additionally, a simple and efficient analytical HPLC method was developed to simultaneously determine the concentration of clotrimazole and itraconazole in the novel microemulsion. The developed method proved to be efficient, robust, and reproducible for both components of the microemulsion. We also performed an accelerated stability study of this formulation, and the developed analytical method was applied to monitor the content of active ingredients. Interestingly, these investigations led to the detection of a known clotrimazole degradation product whose structure was confirmed using NMR and HRMS, as well as a possible interaction between itraconazole and benzyl alcohol. Full article
(This article belongs to the Special Issue Analytical Methods for Toxics Determination)
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13 pages, 905 KiB  
Article
Effect of Anti-Clouding Agent on the Fate of 3-Monochloropropane-1,2-Diol Esters and Glycidyl Esters in Palm Olein during Repeated Frying
by Azmil Haizam Ahmad Tarmizi, Raznim Arni Abd Razak, Abdul Niefaizal Abdul Hammid and Ainie Kuntom
Molecules 2019, 24(12), 2332; https://doi.org/10.3390/molecules24122332 - 25 Jun 2019
Cited by 18 | Viewed by 4230
Abstract
Issues on 3-monochloropropane-diol-1,2-diol (MCPD) esters and glycidyl esters in refined oil have gained much attention when these heat-induced contaminants are associated with health implications. Oil that undergoes the frying process could influence the fates of 3-MCPD esters and glycidyl esters, especially with the [...] Read more.
Issues on 3-monochloropropane-diol-1,2-diol (MCPD) esters and glycidyl esters in refined oil have gained much attention when these heat-induced contaminants are associated with health implications. Oil that undergoes the frying process could influence the fates of 3-MCPD esters and glycidyl esters, especially with the addition of an anti-clouding agent. In this study, we investigated the effect of polyglycerol fatty acid esters (PGE) on the transients of 3-MCPD esters and glycidyl esters in palm olein (POo) during intermittent frying. Thermal resistance of POo fortified with PGE (0.1% to 0.4%) was assessed for 8 h of daily frying operations at 180 °C across five consecutive days. The addition of PGE decelerated the reduction of 3-MCPD esters and glycidyl esters with the progression of frying. The presence of these compounds coincided with the amount of oil taken up by the fried product. The inclusion of PGE in POo also induced higher augmentation of polar compound fractions, i.e., oxidised triacylglycerols (OxTAG) and polymerised triacylglycerols (PTAG), but gave comparable free fatty acid (FFA), p-anisidine value (AnV), total chloride and fatty acid composition (FAC) with control oil (POo). The results also showed that the presence of chloride in POo did not onset further formation of 3-MCPD esters and glycidyl esters throughout the frying period. As the behaviours of 3-MCPD esters and glycidyl esters were affected by PGE, only a sufficient amount should be added into POo to ensure oil clarity at a realistic period. Full article
(This article belongs to the Special Issue Chemistry & Health)
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31 pages, 6392 KiB  
Article
Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen Synthase Kinase-3β Inhibitors
by Stanislav Andreev, Tatu Pantsar, Francesco Ansideri, Mark Kudolo, Michael Forster, Dieter Schollmeyer, Stefan A. Laufer and Pierre Koch
Molecules 2019, 24(12), 2331; https://doi.org/10.3390/molecules24122331 - 25 Jun 2019
Cited by 11 | Viewed by 6034
Abstract
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H [...] Read more.
Glycogen synthase kinase-3β (GSK-3β) represents a relevant drug target for the treatment of neurodegenerative pathologies including Alzheimer’s disease. We herein report on the optimization of a novel class of GSK-3β inhibitors based on the tofacitinib-derived screen hit 3-((3R,4R)-3-((7-chloro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino)-4-methylpiperidin-1-yl)-3-oxopropanenitrile (1). We synthesized a series of 19 novel 7-chloro-9H-pyrimido[4,5-b]indole-based derivatives and studied their structure–activity relationships with focus on the cyanoacetyl piperidine moiety. We unveiled the crucial role of the nitrile group and its importance for the activity of this compound series. A successful rigidization approach afforded 3-(3aRS,7aSR)-(1-(7-chloro-9H-pyrimido[4,5-b]indol-4-yl)octahydro-6H-pyrrolo[2,3-c]pyridin-6-yl)-propanenitrile (24), which displayed an IC50 value of 130 nM on GSK-3β and was further characterized by its metabolic stability. Finally, we disclosed the putative binding modes of the most potent inhibitors within the ATP binding site of GSK-3β by 1 µs molecular dynamics simulations. Full article
(This article belongs to the Special Issue Kinase Inhibitors II)
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23 pages, 1278 KiB  
Article
Metabolic Profiling of Water-Soluble Compounds from the Extracts of Dark Septate Endophytic Fungi (DSE) Isolated from Scots Pine (Pinus sylvestris L.) Seedlings Using UPLC–Orbitrap–MS
by Jenni Tienaho, Maarit Karonen, Riina Muilu–Mäkelä, Kristiina Wähälä, Eduardo Leon Denegri, Robert Franzén, Matti Karp, Ville Santala and Tytti Sarjala
Molecules 2019, 24(12), 2330; https://doi.org/10.3390/molecules24122330 - 25 Jun 2019
Cited by 23 | Viewed by 5059 | Correction
Abstract
Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi [...] Read more.
Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi belonged to dark septate endophytes (DSE). The metabolic profiles of the hot water extracts of the fungi were investigated using Ultrahigh Performance Liquid Chromatography with Diode Array Detection and Electron Spray Ionization source Mass Spectrometry with Orbitrap analyzer (UPLC–DAD–ESI–MS–Orbitrap). Out of 318 metabolites, we were able to identify 220, of which a majority was amino acids and peptides. Additionally, opine amino acids, amino acid quinones, Amadori compounds, cholines, nucleobases, nucleosides, nucleotides, siderophores, sugars, sugar alcohols and disaccharides were found, as well as other previously reported metabolites from plants or endophytes. Some differences of the metabolic profiles, regarding the amount and identity of the found metabolites, were observed even though the fungi were isolated from the same host. Many of the discovered metabolites have been described possessing biological activities and properties, which may make a favorable contribution to the host plant nutrient availability or abiotic and biotic stress tolerance. Full article
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11 pages, 2062 KiB  
Article
Purification, Characterization, Prebiotic Preparations and Antioxidant Activity of Oligosaccharides from Mulberries
by Erna Li, Shiyuan Yang, Yuxiao Zou, Weiwei Cheng, Bing Li, Tenggen Hu, Qian Li, Weifei Wang, Sentai Liao and Daorui Pang
Molecules 2019, 24(12), 2329; https://doi.org/10.3390/molecules24122329 - 25 Jun 2019
Cited by 27 | Viewed by 4063
Abstract
A water-soluble oligosaccharide termed EMOS-1a was prepared by enzymatic hydrolysis of polysaccharides purified from mulberries by column chromatography. The chemical structure of the purified fraction was investigated by ultraviolet spectroscopy, Fourier-transform infrared spectroscopy, and gas chromatography–mass spectrometry, which indicated that galactose was the [...] Read more.
A water-soluble oligosaccharide termed EMOS-1a was prepared by enzymatic hydrolysis of polysaccharides purified from mulberries by column chromatography. The chemical structure of the purified fraction was investigated by ultraviolet spectroscopy, Fourier-transform infrared spectroscopy, and gas chromatography–mass spectrometry, which indicated that galactose was the main constituent of EMOS-1a. Chemical analyses showed that the uronic acid and sulfate content of EMOS-1a were 5.6% and 8.35%, respectively, while gel permeation chromatography showed that EMOS-1a had an average molecular weight of 987 Da. The antioxidant activities of EMOS-1a were next investigated, and EMOS-1a exhibited concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, Trolox equivalent antioxidant capacity, and ferric reducing antioxidant power. The level of proliferation of Lactobacillus rhamnosus reached 1420 ± 16% when 4% (w/v) EMOS-1a was added, where the number of colonies in MRS (de Man, Rogosa, and Sharpe) medium with no added oligosaccharide was defined as 100% proliferation. These results indicate that the oligosaccharide EMOS-1a could be used as a natural antioxidant in prebiotic preparations. Full article
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33 pages, 3134 KiB  
Article
Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights
by Salem El Kharrat, Philippe Laurent, Laurent Boiteau and Hubert Blancou
Molecules 2019, 24(12), 2328; https://doi.org/10.3390/molecules24122328 - 25 Jun 2019
Cited by 3 | Viewed by 4403
Abstract
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of [...] Read more.
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it. Full article
(This article belongs to the Collection Heterocyclic Compounds)
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11 pages, 2254 KiB  
Article
Anomeric Spironucleosides of β-d-Glucopyranosyl Uracil as Potential Inhibitors of Glycogen Phosphorylase
by Aggeliki Stathi, Michael Mamais, Evangelia D. Chrysina and Thanasis Gimisis
Molecules 2019, 24(12), 2327; https://doi.org/10.3390/molecules24122327 - 25 Jun 2019
Cited by 8 | Viewed by 3250
Abstract
In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) may prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry [...] Read more.
In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) may prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function (e.g., inhibition of GP). For this study, the Suárez radical methodology was successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not previously constructed via a radical pathway, starting from 6-hydroxymethyl-β-d-glucopyranosyluracil. It was shown that, in the rigid pyranosyl conformation, the required [1,5]-radical translocation was a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the 1H-NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb. Full article
(This article belongs to the Special Issue Biomimetic Radical Chemistry and Applications)
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18 pages, 3274 KiB  
Article
Optimization of Light Intensity and NaNO3 Concentration in Amazon Cyanobacteria Cultivation to Produce Biodiesel
by Joseline Barbosa Aboim, Deborah Terra de Oliveira, Vanessa Albuquerque de Mescouto, André Silva dos Reis, Geraldo Narciso da Rocha Filho, Agenor Valadares Santos, Luciana Pereira Xavier, Alberdan Silva Santos, Evonnildo Costa Gonçalves and Luis Adriano Santos do Nascimento
Molecules 2019, 24(12), 2326; https://doi.org/10.3390/molecules24122326 - 24 Jun 2019
Cited by 20 | Viewed by 3985
Abstract
The objective of this study, for the first time, was to optimize Amazonian cyanobacterial culture conditions for improving cell productivity and lipid content, by analyzing the effect of light intensity and nitrogen concentration, for empirically evaluating biodiesel quality parameters. The strains Synechocystis sp. [...] Read more.
The objective of this study, for the first time, was to optimize Amazonian cyanobacterial culture conditions for improving cell productivity and lipid content, by analyzing the effect of light intensity and nitrogen concentration, for empirically evaluating biodiesel quality parameters. The strains Synechocystis sp. CACIAM05, Microcystis aeruginosa CACIAM08, Pantanalinema rosaneae CACIAM18, and Limnothrix sp. CACIAM25, were previously identified by morphological and molecular analysis (16S rRNA) and were selected based on their production of chlorophyll a and dry cell weight. Then, factorial planning (22) with central points was applied, with light intensity and NaNO3 concentration as independent variables. As response variables, cell productivity and lipid content were determined. Statistical analysis indicated that for all strains, the independent variables were statistically significant for cell productivity. Analysis of the fatty acid composition demonstrated diversity in the composition of the fatty acid profile from the experimental planning assays of each strain. The Biodiesel Analyzer software predicted the biodiesel quality parameters. CACIAM05 and CACIAM25 obtained better parameters with low levels of light intensity and NaNO3 concentration, whereas CACIAM08 and CACIAM18 obtained better parameters with low NaNO3 concentrations and high luminous intensity. Full article
(This article belongs to the Special Issue Microalgae for Production of Bioproducts and Biofuels)
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15 pages, 1169 KiB  
Article
Development of a Sustainable, Simple, and Robust Method for Efficient l-DOPA Extraction
by Katarzyna Polanowska, Rafal M. Łukasik, Maciej Kuligowski and Jacek Nowak
Molecules 2019, 24(12), 2325; https://doi.org/10.3390/molecules24122325 - 24 Jun 2019
Cited by 28 | Viewed by 5649
Abstract
l-3,4-dihydroxyphenylalanine (l-DOPA) is a medically relevant compound in Parkinson’s disease therapy. Several extraction methods of l-DOPA from beans, including velvet and faba beans, have been described in the literature. However, these methods require the use of strong acids, long [...] Read more.
l-3,4-dihydroxyphenylalanine (l-DOPA) is a medically relevant compound in Parkinson’s disease therapy. Several extraction methods of l-DOPA from beans, including velvet and faba beans, have been described in the literature. However, these methods require the use of strong acids, long extraction times, or complex downstream processing, which makes the extraction of l-DOPA expensive and energy-demanding, limiting its industrial application. In addition, the stability of l-DOPA during the extraction process is critical, further complicating the extraction of adequate amounts of this amino acid. This work is the first report on a simple, rapid, greener, and robust extraction method of l-DOPA. The developed method consists of a quick homogenization step followed by a double extraction with 0.2% v/v acetic acid for 20 min and was applied to faba bean at a ratio of 1:25 with respect to the extracting solvent. This study also investigated the stability of l-DOPA during extraction and thermal treatment. The proposed method demonstrated to be robust and extraordinarily efficient for numerous cultivars of faba bean, velvet bean, and food products containing faba beans. Full article
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10 pages, 1953 KiB  
Article
Amorphous Carbon Generation as a Photocatalytic Reaction on DNA-Assembled Gold and Silver Nanostructures
by Christian Heck, Yuya Kanehira, Janina Kneipp and Ilko Bald
Molecules 2019, 24(12), 2324; https://doi.org/10.3390/molecules24122324 - 24 Jun 2019
Cited by 21 | Viewed by 5430
Abstract
Background signals from in situ-formed amorphous carbon, despite not being fully understood, are known to be a common issue in few-molecule surface-enhanced Raman scattering (SERS). Here, discrete gold and silver nanoparticle aggregates assembled by DNA origami were used to study the conditions for [...] Read more.
Background signals from in situ-formed amorphous carbon, despite not being fully understood, are known to be a common issue in few-molecule surface-enhanced Raman scattering (SERS). Here, discrete gold and silver nanoparticle aggregates assembled by DNA origami were used to study the conditions for the formation of amorphous carbon during SERS measurements. Gold and silver dimers were exposed to laser light of varied power densities and wavelengths. Amorphous carbon prevalently formed on silver aggregates and at high power densities. Time-resolved measurements enabled us to follow the formation of amorphous carbon. Silver nanolenses consisting of three differently-sized silver nanoparticles were used to follow the generation of amorphous carbon at the single-nanostructure level. This allowed observation of the many sharp peaks that constitute the broad amorphous carbon signal found in ensemble measurements. In conclusion, we highlight strategies to prevent amorphous carbon formation, especially for DNA-assembled SERS substrates. Full article
(This article belongs to the Special Issue Emerging Trend in DNA Nanotechnology)
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14 pages, 816 KiB  
Review
Advances in Biosynthesis, Pharmacology, and Pharmacokinetics of Pinocembrin, a Promising Natural Small-Molecule Drug
by Xiaoling Shen, Yeju Liu, Xiaoya Luo and Zhihong Yang
Molecules 2019, 24(12), 2323; https://doi.org/10.3390/molecules24122323 - 24 Jun 2019
Cited by 74 | Viewed by 7241
Abstract
Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy [...] Read more.
Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy and a two-phase pH fermentation strategy. Pinocembrin poses an interest for its remarkable pharmacological activities, such as neuroprotection, anti-oxidation, and anti-inflammation. Studies have shown that pinocembrin works excellently in treating ischemic stroke. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Given its significant efficacy in cerebral ischemia, pinocembrin has been approved by China Food and Drug Administration (CFDA) as a new treatment drug for ischemic stroke and is currently in progress in phase II clinical trials. Research has shown that pinocembrin can be absorbed rapidly in the body and easily cross the blood–brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body. Pinocembrin has also been found to play a role in Parkinson’s disease, Alzheimer’s disease, and specific solid tumors, but its mechanisms of action require in-depth studies. In this review, we summarized the latest 10 years of studies on the biosynthesis, pharmacological activities, and pharmacokinetics of pinocembrin, focusing on its effects on certain diseases, aiming to explore its targets, explaining possible mechanisms of action, and finding potential therapeutic applications. Full article
(This article belongs to the Special Issue Synthesis, Study and Utilization of Natural Products)
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17 pages, 3076 KiB  
Article
Niosomal Nanocarriers for Enhanced Skin Delivery of Quercetin with Functions of Anti-Tyrosinase and Antioxidant
by Banyi Lu, Yanting Huang, Zhongyun Chen, Jingyi Ye, Hongyu Xu, Wenrong Chen and Xiaoying Long
Molecules 2019, 24(12), 2322; https://doi.org/10.3390/molecules24122322 - 24 Jun 2019
Cited by 77 | Viewed by 5949
Abstract
This study aimed to screen an effective flavonoid with promising whitening and antioxidant capacities, and design flavonoid-loaded niosomes to improve its solubility, stability, and penetration. In vitro anti-tyrosinase and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiments were conducted to investigate the whitening and antioxidant [...] Read more.
This study aimed to screen an effective flavonoid with promising whitening and antioxidant capacities, and design flavonoid-loaded niosomes to improve its solubility, stability, and penetration. In vitro anti-tyrosinase and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiments were conducted to investigate the whitening and antioxidant capacities of several flavonoids, including quercetin, morin, festin, myricetin, rutin, and breviscapine. The conductivity, viscosity, and particle size of Span60-RH40-based formulation of nonionic surfactant vesicles (niosomes) with different mass ratios were studied to determine the most appropriate formulation. Drug-loaded niosomes were characterized for size, zeta potential, morphology, and entrapment efficiency. The photostability, solubility, release behavior, ex vivo drug penetration, and skin retention were also studied. The results showed that quercetin has considerable whitening and antioxidant capacities and Span60-RH40 at a mass ratio of 9:11 forms spherical or oval niosomes of 97.6 ± 3.1 nm with a zeta potential range of 31.1 ± 0.9 mV, and drug entrapment efficiency as high as 87.3 ± 1.6%. Niosomes remarkably improved the solubility and photostability of quercetin. Furthermore, compared to quercetin solution, quercetin-niosomes had the advantages of sustained release and improved transdermal penetration, with skin retention 2.95 times higher than quercetin solution. Full article
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29 pages, 9166 KiB  
Article
Discovery of Novel UV-Filters with Favorable Safety Profiles in the 5-Arylideneimidazolidine-2,4-dione Derivatives Group
by Justyna Popiół, Agnieszka Gunia-Krzyżak, Kamil Piska, Dorota Żelaszczyk, Paulina Koczurkiewicz, Karolina Słoczyńska, Katarzyna Wójcik-Pszczoła, Anna Krupa, Agata Kryczyk-Poprawa, Ewa Żesławska, Wojciech Nitek, Paweł Żmudzki, Henryk Marona and Elżbieta Pękala
Molecules 2019, 24(12), 2321; https://doi.org/10.3390/molecules24122321 - 24 Jun 2019
Cited by 10 | Viewed by 4431
Abstract
Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine [...] Read more.
Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,2′-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,2′-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo- imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPFin vitro of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 µM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model. Full article
(This article belongs to the Section Medicinal Chemistry)
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15 pages, 2937 KiB  
Article
Copper Nanowires Modified with Graphene Oxide Nanosheets for Simultaneous Voltammetric Determination of Ascorbic Acid, Dopamine and Acetaminophen
by Wanting Hao, Yuchan Zhang, Jingchuan Fan, Handeng Liu, Qi Shi, Weichi Liu, Qianyu Peng and Guangchao Zang
Molecules 2019, 24(12), 2320; https://doi.org/10.3390/molecules24122320 - 24 Jun 2019
Cited by 21 | Viewed by 4032
Abstract
Copper nanowires (Cu NWs) were modified with graphene oxide (GO) nanosheets to obtain a sensor for simultaneous voltammetric determination of ascorbic acid (AA), dopamine (DA) and acetaminophen (AC). The nanocomposite was obtained via sonication, and its structures were characterized by scanning electron microscopy [...] Read more.
Copper nanowires (Cu NWs) were modified with graphene oxide (GO) nanosheets to obtain a sensor for simultaneous voltammetric determination of ascorbic acid (AA), dopamine (DA) and acetaminophen (AC). The nanocomposite was obtained via sonication, and its structures were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS). The electrochemical oxidation activity of the materials (placed on a glassy carbon electrode) was studied by cyclic voltammetry and differential pulse voltammetry. Due to the synergistic effect of Cu NWs and GO, the specific surface, electrochemical oxidation performance and conductivity are improved when compared to each individual component. The peaks for AA (−0.08 V), DA (+0.16 V), and AC (+0.38 V) are well separated. The sensor has wide linear ranges which are from 1–60 μM, 1–100 μM, and 1–100 μM for AA, DA, and AC, respectively, when operated in the differential pulse voltammetric mode. The detection limits are 50, 410 and 40 nM, respectively. Potential interferences by uric acid (20 μM), glucose (10 mM), NaCl (1 mM), and KCl (1 mM) were tested for AA (1 μΜ), DA (1 μΜ), and AC (1 μΜ) and were found to be insignificant. The method was successfully applied to the quantification of AA, DA, and AC in spiked serum samples. Full article
(This article belongs to the Special Issue Recent Advances of Bioanalytical Electrochemistry of Molecules)
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11 pages, 4157 KiB  
Comment
Comment on: Synthesis of New Azo Compounds Based on N-(4-Hydroxyphenyl)maleimide and N-(4-Methylphenyl)maleimide. Molecules 2010, 15, 7498–7508
by John J. Morrison, Viktoria K. Brandt and Stephen G. Yeates
Molecules 2019, 24(12), 2319; https://doi.org/10.3390/molecules24122319 - 23 Jun 2019
Cited by 2 | Viewed by 4354
Abstract
The synthesis of (E)-phenylazo-3-N-(4-hydroxyphenyl)maleimide (1) using a procedure previously reported in Molecules is deemed to be erroneous. A detailed re-investigation of the earlier work suggests that the spectral data for key intermediates and the final product, ( [...] Read more.
The synthesis of (E)-phenylazo-3-N-(4-hydroxyphenyl)maleimide (1) using a procedure previously reported in Molecules is deemed to be erroneous. A detailed re-investigation of the earlier work suggests that the spectral data for key intermediates and the final product, (1), was mis-assigned. We conclude that compound (1) was not synthesized, but rather an unusual ring opening reaction of the maleimide unit of the starting material, N-(4-hydroxyphenyl)maleimide (2) leading to the generation of (Z)-4-((4-hydroxyphenyl)amino)-4-oxobut-2-enoic acid, (3) was observed instead. Examination of the original experimental data reveals systematic errors in the reporting of all of the combustion microanalytical data. Overall, the present investigation suggests that errors in the interpretation of spectral data, falsification of analytical data and selective editing of experimental results raise questions over the veracity of the work presented in the original paper. Full article
(This article belongs to the Section Organic Chemistry)
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15 pages, 1902 KiB  
Article
A Mass Spectrometric Study on Tannin Degradation within Dyed Woolen Yarns
by Ilaria Degano, Marco Mattonai, Francesca Sabatini and Maria Perla Colombini
Molecules 2019, 24(12), 2318; https://doi.org/10.3390/molecules24122318 - 22 Jun 2019
Cited by 20 | Viewed by 4441
Abstract
Natural tannins from various plants have been used throughout human history in textile dyeing, often as mordant dyes. The ageing behavior of these dyes is a challenge in conservation science, requiring a thorough knowledge of the textile–mordant-dye system. In this work, we analyzed [...] Read more.
Natural tannins from various plants have been used throughout human history in textile dyeing, often as mordant dyes. The ageing behavior of these dyes is a challenge in conservation science, requiring a thorough knowledge of the textile–mordant-dye system. In this work, we analyzed reference wool yarns dyed with natural tannins from oak gallnuts, walnut (Juglans regia), and catechu (Acacia catechu), after artificial ageing. To gain insights on the composition of the dyestuffs and on how they aged, an analytical procedure based on extraction with Na2EDTA/DMF (ethylenediaminetetraacetic acid/dimethylformamide) and high-performance liquid chromatography (HPLC) analysis using high-resolution mass spectrometry detection was used. Since conventional reversed-phase (RP) columns usually show poor retention efficiency of highly polar compounds such as tannins, an RP-amide embedded polar group stationary phase was used to achieve optimal retention of the most polar compounds. Tannins from oak gallnuts showed little degradation after ageing, while a significant increase in the content of hydroxybenzoic acids was observed for tannins from walnut and catechu. Finally, the analytical procedure was applied to characterize the tannin dyes in historical tapestries from the 15th to 16th century, and the results were discussed in comparison with the reference yarns. Full article
(This article belongs to the Special Issue Natural Dyes)
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22 pages, 2152 KiB  
Review
Cytotoxic Effects of Diterpenoid Alkaloids Against Human Cancer Cells
by Koji Wada and Hiroshi Yamashita
Molecules 2019, 24(12), 2317; https://doi.org/10.3390/molecules24122317 - 22 Jun 2019
Cited by 39 | Viewed by 6379
Abstract
Diterpenoid alkaloids are isolated from plants of the genera Aconitum, Delphinium, and Garrya (Ranunculaceae) and classified according to their chemical structures as C18-, C19- or C20-diterpenoid alkaloids. The extreme toxicity of certain compounds, e.g., aconitine, [...] Read more.
Diterpenoid alkaloids are isolated from plants of the genera Aconitum, Delphinium, and Garrya (Ranunculaceae) and classified according to their chemical structures as C18-, C19- or C20-diterpenoid alkaloids. The extreme toxicity of certain compounds, e.g., aconitine, has prompted a thorough investigation of how structural features affect their bioactivities. Therefore, natural diterpenoid alkaloids and semi-synthetic alkaloid derivatives were evaluated for cytotoxic effects against human tumor cells [A549 (lung carcinoma), DU145 (prostate carcinoma), MDA-MB-231 (triple-negative breast cancer), MCF-7 (estrogen receptor-positive, HER2-negative breast cancer), KB (identical to cervical carcinoma HeLa derived AV-3 cell line), and multidrug-resistant (MDR) subline KB-VIN]. Among the tested alkaloids, C19-diterpenoid (e.g., lipojesaconitine, delcosine and delpheline derivatives) and C20-diterpenoid (e.g., kobusine and pseudokobusine derivatives) alkaloids exhibited significant cytotoxic activity and, thus, provide promising new leads for further development as antitumor agents. Notably, several diterpenoid alkaloids were more potent against MDR subline KB-VIN cells than the parental drug-sensitive KB cells. Full article
(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)
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