Molecules

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Open AccessReview

Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer

by Bowen Du and Joong Sup Shim

Molecules 2016, 21(7), 965; https://doi.org/10.3390/molecules21070965 - 22 Jul 2016

Cited by 601 | Viewed by 29543

Epithelial–mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous [...] Read more.

Epithelial–mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous EMT-related signaling pathways are involved in drug resistance in cancer cells. Cells undergoing EMT show a feature similar to cancer stem cells (CSCs), such as an increase in drug efflux pumps and anti-apoptotic effects. Therefore, targeting EMT has been considered a novel opportunity to overcome cancer drug resistance. This review describes the mechanism by which EMT contributes to drug resistance in cancer cells and summarizes new advances in research in EMT-associated drug resistance. Full article

(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)

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6668 KiB

Open AccessReview

Immobilized Lignin Peroxidase-Like Metalloporphyrins as Reusable Catalysts in Oxidative Bleaching of Industrial Dyes

by Paolo Zucca, Cláudia M. B. Neves, Mário M. Q. Simões, Maria Da Graça P. M. S. Neves, Gianmarco Cocco and Enrico Sanjust

Molecules 2016, 21(7), 964; https://doi.org/10.3390/molecules21070964 - 22 Jul 2016

Cited by 51 | Viewed by 10681

Abstract

Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and [...] Read more.

Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and nitroso-compounds, has been deeply investigated. Such a broad substrate specificity has suggested their use also in the bleaching of textile plant wastewaters. In fact, industrial dyes belong to very different chemical classes, being their effective and inexpensive oxidation an important challenge from both economic and environmental perspective. Accordingly, we review here the most widespread synthetic metalloporphyrins, and the most promising formulations for large-scale applications. In particular, we focus on the most convenient approaches for immobilization to conceive economical affordable processes. Then, the molecular routes of catalysis and the reported substrate specificity on the treatment of the most diffused textile dyes are encompassed, including the use of redox mediators and the comparison with the most common biological and enzymatic alternative, in order to depict an updated picture of a very promising field for large-scale applications. Full article

(This article belongs to the Special Issue Tetrapyrrolic Macrocycles: Synthesis, Functionalization and Applications)

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2080 KiB

Open AccessArticle

Synthesis, Characterization, and Retinol Stabilization of Fatty Amide-β-cyclodextrin Conjugates

by Hwanhee Kim, Yiluo Hu, Daham Jeong, Bong-Hyun Jun, Eunae Cho and Seunho Jung

Molecules 2016, 21(7), 963; https://doi.org/10.3390/molecules21070963 - 22 Jul 2016

Cited by 10 | Viewed by 8150

Abstract

Amphiphilic cyclodextrin (CD) has been the object of growing scientific attention because of its two recognition sites, the cavity and the apolar heart, formed by self-assembly. In the present study, mono[6-deoxy-6-(octadecanamido)]-β-CD and mono[6-deoxy-6-(octadecenamido)]-β-CD were successfully synthesized by reacting mono-6-amino-6-deoxy-β-CD with N-hydroxysuccinimide esters [...] Read more.

Amphiphilic cyclodextrin (CD) has been the object of growing scientific attention because of its two recognition sites, the cavity and the apolar heart, formed by self-assembly. In the present study, mono[6-deoxy-6-(octadecanamido)]-β-CD and mono[6-deoxy-6-(octadecenamido)]-β-CD were successfully synthesized by reacting mono-6-amino-6-deoxy-β-CD with N-hydroxysuccinimide esters of corresponding fatty acids in DMF. The structures were analyzed using nuclear magnetic resonance spectroscopy and mass spectrometry. The amphiphilic β-CDs were able to form self-assembled nano-vesicles in water, and the supramolecular architectures were characterized using fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Using the cavity-type nano-vesicles, all-trans-retinol was efficiently encapsulated; it was then stabilized against the photo-degradation. Therefore, the present fatty amide-β-CD conjugate will be a potential molecule for carrier systems in cosmetic and pharmaceutical applications. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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Open AccessArticle

Two New Pentacyclic Triterpene Saponins from the Leaves of Akebia trifoliata

by Qiao-Lin Xu, Jing Wang, Li-Mei Dong, Qiang Zhang, Bi Luo, Yong-Xia Jia, Hong-Feng Wang and Jian-Wen Tan

Molecules 2016, 21(7), 962; https://doi.org/10.3390/molecules21070962 - 22 Jul 2016

Cited by 20 | Viewed by 5372

Abstract

Two new pentacyclic triterpene saponins, named akebiaoside K (1) and akebiaoside N (2), were isolated from the leaves of Akebia trifoliata, together with five known triterpenoids 3–7. They were all isolated from the leaves of [...] Read more.

Two new pentacyclic triterpene saponins, named akebiaoside K (1) and akebiaoside N (2), were isolated from the leaves of Akebia trifoliata, together with five known triterpenoids 3–7. They were all isolated from the leaves of A. trifoliata for the first time. Their structures were established by spectral and chemical means. Triterpenes 5 and 7 were found to show moderate in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC₅₀ values ranging from 0.023 to 0.038 mM. Triterpenes 5–7 were further revealed to show significant in vitro α-glucosidase inhibitory activity with IC₅₀ values from 0.040 to 0.220 mM, making them more potent than the reference compound acarbose (IC₅₀ 0.409 mM). Meanwhile, no obvious inhibitory effects were observed for the isolated triterpene saponins 1–4 in both bioactivity assays. Full article

(This article belongs to the Section Natural Products Chemistry)

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4053 KiB

Open AccessArticle

Chlorophyll a Covalently Bonded to Organo-Modified Translucent Silica Xerogels: Optimizing Fluorescence and Maximum Loading

by M. A. García-Sánchez, I. N. Serratos, R. Sosa, T. Tapia-Esquivel, F. González-García, F. Rojas-González, S. R. Tello-Solís, A. Y. Palacios-Enriquez, J. M. Esparza Schulz and A. Arrieta

Molecules 2016, 21(7), 961; https://doi.org/10.3390/molecules21070961 - 22 Jul 2016

Cited by 6 | Viewed by 6723

Abstract

Chlorophyll is a pyrrolic pigment with important optical properties, which is the reason it has been studied for many years. Recently, interest has been rising with respect to this molecule because of its outstanding physicochemical properties, particularly applicable to the design and development [...] Read more.

Chlorophyll is a pyrrolic pigment with important optical properties, which is the reason it has been studied for many years. Recently, interest has been rising with respect to this molecule because of its outstanding physicochemical properties, particularly applicable to the design and development of luminescent materials, hybrid sensor systems, and photodynamic therapy devices for the treatment of cancer cells and bacteria. More recently, our research group has been finding evidence for the possibility of preserving these important properties of substrates containing chlorophyll covalently incorporated within solid pore matrices, such as SiO₂, TiO₂ or ZrO₂ synthesized through the sol-gel process. In this work, we study the optical properties of silica xerogels organo-modified on their surface with allyl and phenyl groups and containing different concentrations of chlorophyll bonded to the pore walls, in order to optimize the fluorescence that these macrocyclic species displays in solution. The intention of this investigation was to determine the maximum chlorophyll a concentration at which this molecule can be trapped inside the pores of a given xerogel and to ascertain if this pigment remains trapped as a monomer, a dimer, or aggregate. Allyl and phenyl groups were deposited on the surface of xerogels in view of their important effects on the stability of the molecule, as well as over the fluorescence emission of chlorophyll; however, these organic groups allow the trapping of either chlorophyll a monomers or dimers. The determination of the above parameters allows finding the most adequate systems for subsequent in vitro or in vivo studies. The characterization of the obtained xerogels was performed through spectroscopic absorption, emission and excitation spectra. These hybrid systems can be employed as mimics of natural systems; the entrapment of chlorophyll inside pore matrices indicates that it is possible to exploit some of the most physicochemical properties of trapped chlorophyll for diverse technological applications. The data herein collected suggest the possibility of applying the developed methodology to other active, captive molecules in order to synthesize new hybrid materials with optimized properties, suitable to be applied in diverse technological fields. Full article

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Open AccessShort Note

Colour Evaluation, Bioactive Compound Content, Phenolic Acid Profiles and in Vitro Biological Activity of Passerina del Frusinate White Wines: Influence of Pre-Fermentative Skin Contact Times

by Katya Carbone and Luciano Fiordiponti

Molecules 2016, 21(7), 960; https://doi.org/10.3390/molecules21070960 - 22 Jul 2016

Cited by 7 | Viewed by 5545

Abstract

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in [...] Read more.

Passerina del Frusinate is an autochthonous wine grape variety, which grows in the Lazio region that is currently being evaluated by local wine producers. In this study, colour properties (CIELab coordinates), bioactive compounds (total polyphenols and flavan-3-ols), HPLC-DAD phenolic acid profiles and in vitro biological activity of monovarietal Passerina del Frusinate white wines and the effect of different maceration times (0, 18 and 24 h) were evaluated based on these parameters. Results highlighted statistically significant differences for almost all analysed parameters due to a strong influence of the pre-fermentative skin contact time. The flavan content of macerated wines was six times higher than that of the control, while total polyphenols were 1.5 times higher. According to their phytochemical content, macerated wines showed the highest antiradical capacity tested by means of DPPH^• and ABTS^+• assays. Besides, prolonged maceration resulted in a reduction of CIELab coordinates as well as of the content of phenolic substances and antiradical capacity. Among the phenolic acids analysed, the most abundant were vanillic acid and caffeic acid; the latter proved to be the most susceptible to degradation as a result of prolonged maceration. Passerina del Frusinate appears as a phenol-rich white wine with a strong antioxidant potential similar to that of red wines. Full article

(This article belongs to the Collection Wine Chemistry)

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Open AccessArticle

New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity

by Dorota G. Piotrowska, Graciela Andrei, Dominique Schols, Robert Snoeck and Magdalena Grabkowska-Drużyc

Molecules 2016, 21(7), 959; https://doi.org/10.3390/molecules21070959 - 22 Jul 2016

Cited by 19 | Viewed by 6385

Abstract

A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. [...] Read more.

A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC₅₀ = 6.84, 15.29 and 9.44 μM) toward VZV (TK⁺ strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC₅₀ = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC₅₀ in the 21–102 μM range. Full article

(This article belongs to the Section Medicinal Chemistry)

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4167 KiB

Open AccessReview

Metabolic Responses of Bacterial Cells to Immobilization

by Joanna Żur, Danuta Wojcieszyńska and Urszula Guzik

Molecules 2016, 21(7), 958; https://doi.org/10.3390/molecules21070958 - 22 Jul 2016

Cited by 149 | Viewed by 12468

Abstract

In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state [...] Read more.

In recent years immobilized cells have commonly been used for various biotechnological applications, e.g., antibiotic production, soil bioremediation, biodegradation and biotransformation of xenobiotics in wastewater treatment plants. Although the literature data on the physiological changes and behaviour of cells in the immobilized state remain fragmentary, it is well documented that in natural settings microorganisms are mainly found in association with surfaces, which results in biofilm formation. Biofilms are characterized by genetic and physiological heterogeneity and the occurrence of altered microenvironments within the matrix. Microbial cells in communities display a variety of metabolic differences as compared to their free-living counterparts. Immobilization of bacteria can occur either as a natural phenomenon or as an artificial process. The majority of changes observed in immobilized cells result from protection provided by the supports. Knowledge about the main physiological responses occurring in immobilized cells may contribute to improving the efficiency of immobilization techniques. This paper reviews the main metabolic changes exhibited by immobilized bacterial cells, including growth rate, biodegradation capabilities, biocatalytic efficiency and plasmid stability. Full article

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Open AccessArticle

Qingxuan Jiangya Decoction Reverses Vascular Remodeling by Inducing Vascular Smooth Muscle Cell Apoptosis in Spontaneously Hypertensive Rats

by Fei Xiao, Fei He, Hongwei Chen, Shan Lin, Aling Shen, Youqin Chen, Jianfeng Chu and Jun Peng

Molecules 2016, 21(7), 956; https://doi.org/10.3390/molecules21070956 - 22 Jul 2016

Cited by 18 | Viewed by 7168

Abstract

Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the [...] Read more.

Qingxuan Jiangya Decoction (QXJYD), a traditional Chinese medicine formula prescribed by academician Ke-ji Chen, has been used in China to clinically treat hypertension for decades of years. However, the molecular mechanisms of its action remain largely unknown. In this study, we examined the therapeutic efficacy of QXJYD against elevated systolic blood pressure in the spontaneously hypertensive rat (SHR) model, and investigated the underlying molecular mechanisms. We found that oral administration of QXJYD significantly reduced the elevation of systolic blood pressure in SHR but had no effect on body weight change. Additionally, QXJYD treatment significantly decreased the media thickness and ratio of media thickness/lumen diameter in the carotid arteries of SHR. Moreover, QXJYD remarkably promoted apoptosis of vascular smooth muscle cells and reduced the expression of anti-apoptotic B-cell leukemia/lymphoma 2. Furthermore, QXJYD significantly decreased the plasma Angiotensin II level in SHR. Collectively, our findings suggest that reversing vascular remodeling via inducing VSMC apoptosis could be one of the mechanisms whereby QXJYD treats hypertension. Full article

(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)

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Open AccessArticle

Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors

by Sri Devi Sukumaran, Chin Fei Chee, Geetha Viswanathan, Michael J. C. Buckle, Rozana Othman, Noorsaadah Abd. Rahman and Lip Yong Chung

Molecules 2016, 21(7), 955; https://doi.org/10.3390/molecules21070955 - 22 Jul 2016

Cited by 29 | Viewed by 6144

Abstract

A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC₅₀ values of 40–85 µM. Higher activities were generally [...] Read more.

A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC₅₀ values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessErratum

Erratum: Liu, H., et al. Radical Scavenging by Acetone: A New Perspective to Understand Laccase/ABTS Inactivation and to Recover Redox Mediator. Molecules 2015, 20, 19907–19913

by Molecules Editorial Office

Molecules 2016, 21(7), 957; https://doi.org/10.3390/molecules21070957 - 21 Jul 2016

Viewed by 3332

Abstract

The Molecules Editorial Ofﬁce wishes to report the following erratum to this paper [1].[...] Full article

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Open AccessArticle

Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

by Hui Guo, Dongmei Liu, Bin Gao, Xiaohui Zhang, Minli You, Hui Ren, Hongbo Zhang, Hélder A. Santos and Feng Xu

Molecules 2016, 21(7), 954; https://doi.org/10.3390/molecules21070954 - 21 Jul 2016

Cited by 15 | Viewed by 7915

Abstract

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo [...] Read more.

Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC₅₀ values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds. Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

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Open AccessLetter

Carbon Nanotube Based Groundwater Remediation: The Case of Trichloroethylene

by Kshitij C. Jha, Zhuonan Liu, Hema Vijwani, Mallikarjuna Nadagouda, Sharmila M. Mukhopadhyay and Mesfin Tsige

Molecules 2016, 21(7), 953; https://doi.org/10.3390/molecules21070953 - 21 Jul 2016

Cited by 12 | Viewed by 7685

Abstract

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play [...] Read more.

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play in hybrid, membrane, and pure CNT based systems and presents results with the perspective of existing gaps in design strategies. First, current remediation approaches to trichloroethylene (TCE), the most ubiquitous of the COCs, is presented along with examination of forces contributing to adsorption of analogous contaminants at the molecular level. Second, we present results on TCE adsorption and remediation on pure and hybrid CNT systems with a stress on the specific nature of substrate and molecular architecture that would contribute to competitive adsorption. The delineation of intermolecular interactions that contribute to efficient remediation is needed for custom, scalable field design of purification systems for a wide range of contaminants. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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Open AccessArticle

Protective Effect of the Total Flavonoids from Rosa laevigata Michx Fruit on Renal Ischemia-Reperfusion Injury through Suppression of Oxidative Stress and Inflammation

by Lisha Zhao, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Yan Qi and Jinyong Peng

Molecules 2016, 21(7), 952; https://doi.org/10.3390/molecules21070952 - 21 Jul 2016

Cited by 62 | Viewed by 9050 | Correction

Abstract

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against [...] Read more.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against renal IRI. In the present work, a hypoxia/reoxygenation (H/R) model in NRK-52E cells and ischemia-reperfusion model in rats were used. The results showed that the TFs significantly attenuated cell injury and markedly decreased serum creatinine (Cr) and blood urea nitrogen (BUN) levels in rats. Further investigation revealed that the TFs markedly decreased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) and intracellular reactive oxygen species (ROS), up-regulated the levels of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1), down-regulated the levels of Kelch like ECH-associated protein-1 (Keap1) and the nuclear translocation of nuclear factor-κBp65 (NF-κBp65), and decreased the mRNA levels of interleukine-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, inhibiting Sirt1 by siRNA showed that the role of the natural product in protecting renal IRI was significantly attenuated, suggesting that the effect of the extract against renal IRI depended on Sirt1. Taken together, the TFs has significantly nephroprotective effect against IRI by affecting Sirt1/Nrf2/NF-κB signaling pathway, which should be developed as a new therapeutic agent or food additives to treat acute kidney injury in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

by Seung-Mann Paek, Myeonggyo Jeong, Jeyun Jo, Yu Mi Heo, Young Taek Han and Hwayoung Yun

Molecules 2016, 21(7), 951; https://doi.org/10.3390/molecules21070951 - 21 Jul 2016

Cited by 42 | Viewed by 10410

Abstract

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can [...] Read more.

Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)

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Open AccessArticle

Application of Ultrasound in a Closed System: Optimum Condition for Antioxidants Extraction of Blackberry (Rubus fructicosus) Residues

by Quinatzin Y. Zafra-Rojas, Nelly S. Cruz-Cansino, Aurora Quintero-Lira, Carlos A. Gómez-Aldapa, Ernesto Alanís-García, Alicia Cervantes-Elizarrarás, Norma Güemes-Vera and Esther Ramírez-Moreno

Molecules 2016, 21(7), 950; https://doi.org/10.3390/molecules21070950 - 21 Jul 2016

Cited by 15 | Viewed by 6123

Abstract

Blackberry processing generates up to 20% of residues composed mainly of peel, seeds and pulp that are abundant in flavonoids. The objective of this study was to optimize the ultrasound conditions, in a closed system, for antioxidants extraction, using the response surface methodology. [...] Read more.

Blackberry processing generates up to 20% of residues composed mainly of peel, seeds and pulp that are abundant in flavonoids. The objective of this study was to optimize the ultrasound conditions, in a closed system, for antioxidants extraction, using the response surface methodology. Blackberry (Rubus fructicosus) residues were analyzed for total phenolics, total anthocyanins, and antioxidant activity by ABTS and DPPH. The selected independent variables were ultrasound amplitude (X₁: 80%–90%) and extraction time (X₂: 10–15 min), and results were compared with conventional extraction methods. The optimal conditions for antioxidants extraction were 91% amplitude for 15 min. The results for total phenolic content and anthocyanins and antioxidant activity by ABTS and DPPH were of 1201.23 mg gallic acid equivalent (GAE)/100 g dry weight basis (dw); 379.12 mg/100 g·dw; 6318.98 µmol Trolox equivalent (TE)/100 g·dw and 9617.22 µmol TE/100 g·dw, respectively. Compared to solvent extraction methods (water and ethanol), ultrasound achieved higher extraction of all compounds except for anthocyanins. The results obtained demonstrated that ultrasound is an alternative to improve extraction yield of antioxidants from fruit residues such as blackberry. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

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Open AccessArticle

Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells

by Aoife M. McKeon, Alan Egan, Jay Chandanshive, Helena McMahon and Darren M. Griffith

Molecules 2016, 21(7), 949; https://doi.org/10.3390/molecules21070949 - 21 Jul 2016

Cited by 34 | Viewed by 7258 | Correction

Abstract

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is [...] Read more.

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Stability and Degradation of Caffeoylquinic Acids under Different Storage Conditions Studied by High-Performance Liquid Chromatography with Photo Diode Array Detection and High-Performance Liquid Chromatography with Electrospray Ionization Collision-Induced Dissociation Tandem Mass Spectrometry

by Meng Xue, Hang Shi, Jiao Zhang, Qing-Quan Liu, Jun Guan, Jia-Yu Zhang and Qun Ma

Molecules 2016, 21(7), 948; https://doi.org/10.3390/molecules21070948 - 21 Jul 2016

Cited by 65 | Viewed by 8308

Abstract

Caffeoylquinic acids (CQAs) are main constituents in many herbal medicines with various biological and pharmacological effects. However, CQAs will degrade or isomerize when affected by temperature, pH, light, etc. In this study, high-performance liquid chromatography with photodiode array detection (HPLC-PDA) and high-performance liquid [...] Read more.

Caffeoylquinic acids (CQAs) are main constituents in many herbal medicines with various biological and pharmacological effects. However, CQAs will degrade or isomerize when affected by temperature, pH, light, etc. In this study, high-performance liquid chromatography with photodiode array detection (HPLC-PDA) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was utilized to study the stability and degradation of CQAs (three mono-acyl CQAs and four di-acyl CQAs) under various ordinary storage conditions (involving different temperatures, solvents, and light irradiation). The results indicated that the stability of CQAs was mainly affected by temperature and light irradiation, while solvents did not affect it in any obvious way under the conditions studied. Mono-acyl CQAs were generally much more stable than di-acyl CQAs under the same conditions. Meanwhile, the chemical structures of 30 degradation products were also characterized by HPLC-MSⁿ, inferring that isomerization, methylation, and hydrolysis were three major degradation pathways. The result provides a meaningful clue for the storage conditions of CQAs standard substances and samples. Full article

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1278 KiB

Open AccessCommunication

Identification of Chemical Composition of Leaves and Flowers from Paeonia rockii by UHPLC-Q-Exactive Orbitrap HRMS

by Jinhua Li, Gang Kuang, Xiaohu Chen and Rui Zeng

Molecules 2016, 21(7), 947; https://doi.org/10.3390/molecules21070947 - 21 Jul 2016

Cited by 43 | Viewed by 8839

Abstract

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical [...] Read more.

The Paeonia genus, an important source of crude drugs, has been extensively used in traditional Chinese medicine (TCM) to treat cardiovascular and female-related diseases. Although many peony species have been investigated, the study of Paeonia rockii is still quite limited, especially its chemical composition. Here, an advanced ultra-high-performance liquid chromatography (UHPLC) analytical technique combined with Q-Exactive Orbitrap hybrid quadrupole-Orbitrap mass spectrometry utilizing high-resolution full MS and MS/MS scan modes was applied to screen and identify the chemical constituents of this species. As a result, a total of 46 compounds were characterized, including 11 monoterpene glycosides, five phenolic acids, six tannins and 24 flavonoids. Among them, 16 compounds were reported for the first time in Paeonia rockii. Full article

(This article belongs to the Section Natural Products Chemistry)

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1357 KiB

Open AccessArticle

A New Method for the Isolation of Ergosterol and Peroxyergosterol as Active Compounds of Hygrophoropsis aurantiaca and in Vitro Antiproliferative Activity of Isolated Ergosterol Peroxide

by Renata Nowak, Marta Drozd, Ewaryst Mendyk, Marta Lemieszek, Olga Krakowiak, Wanda Kisiel, Wojciech Rzeski and Katarzyna Szewczyk

Molecules 2016, 21(7), 946; https://doi.org/10.3390/molecules21070946 - 21 Jul 2016

Cited by 55 | Viewed by 8895

Abstract

In the present study, ergosterol peroxide and ergosterol were isolated for the first time from fresh fruit bodies of Hygrophoropsis aurantiaca (False Chanterelle). The substances were characterized mainly by spectroscopic methods (¹H-NMR, ¹³C-NMR, DEPT-45, DEPT-90, DEPT-135, 2D-NMR). In our study, [...] Read more.

In the present study, ergosterol peroxide and ergosterol were isolated for the first time from fresh fruit bodies of Hygrophoropsis aurantiaca (False Chanterelle). The substances were characterized mainly by spectroscopic methods (¹H-NMR, ¹³C-NMR, DEPT-45, DEPT-90, DEPT-135, 2D-NMR). In our study, a new specific thin layer chromatographic method was developed for determination of ergosterol and ergosterol peroxide in H. aurantiaca extract. The method is based on the separation of n-hexane extract on silica gel (Silica Gel G) TLC plates using the optimized solvent system toluene/ethyl acetate (3:1; v/v). The main advantages of the developed method are the simplicity of operation and the low cost. The in vitro study results revealed the antiproliferative properties of ergosterol peroxide against LS180 human colon cancer cells. The described effect was attributed both to altered mitochondrial activity and decreased DNA synthesis. Additionally, in the same concentration range the investigated compound was not toxic to CCD 841 CoTr human colon epithelial cells. The present study suggests that fruit bodies of H. aurantiaca have great potential for producing substances and extracts with potential applications in medicine. Full article

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7321 KiB

Open AccessArticle

Intra-Population Variation of Secondary Metabolites in Cistus ladanifer L.

by Cristina Valares Masa, Juan Carlos Alías Gallego, Natividad Chaves Lobón and Teresa Sosa Díaz

Molecules 2016, 21(7), 945; https://doi.org/10.3390/molecules21070945 - 21 Jul 2016

Cited by 12 | Viewed by 6320

Abstract

In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was [...] Read more.

In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was also found to vary quantitatively and qualitatively in response to various environmental factors. In view of these findings, the present work was designed to clarify whether within a single population there are differences among individuals subject to the same environmental conditions. To this end, we analyzed the leaves of 100 individuals of C. ladanifer. The results showed the existence of intrapopulational variation, since, although all the individuals had the same composition of secondary chemistry, the amounts were different. The individuals of a given population of C. ladanifer differ from each other even when growing under similar conditions. According to the ammount of flavonoids and diterpenes observed in each individual, it was possible to distinguish four different groups of individuals. Most individuals, evenly distributed within the population, had low concentrations of the studied compounds, whilst other individuals synthesized greater amounts and were randomly distributed among the former. Given the functions of flavonoids and diterpenes in this species, the quantified intra-population variation may involve greater plasticity for the species in the face of environmental changes. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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356 KiB

Open AccessCommunication

Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities

by Xuekui Xia, Soonok Kim, Changheng Liu and Sang Hee Shim

Molecules 2016, 21(7), 944; https://doi.org/10.3390/molecules21070944 - 20 Jul 2016

Cited by 13 | Viewed by 5481

Abstract

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1–4) and seven α-pyrone analogues (5–10 [...] Read more.

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1–4) and seven α-pyrone analogues (5–10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1–3, 5, and 9–10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC₅₀ of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors. Full article

(This article belongs to the Section Natural Products Chemistry)

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2046 KiB

Open AccessCommunication

Two New Secondary Metabolites from the Endophytic Fungus Endomelanconiopsis endophytica

by Zhang-Hua Sun, Hao-Hua Li, Fa-Liang Liang, Yu-Chan Chen, Hong-Xin Liu, Sai-Ni Li, Guo-Hui Tan and Wei-Min Zhang

Molecules 2016, 21(7), 943; https://doi.org/10.3390/molecules21070943 - 20 Jul 2016

Cited by 7 | Viewed by 5219

Abstract

Two new secondary metabolites, endomeketals A–B (1–2), a new natural product (3), and a known compound (4) were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta [...] Read more.

Two new secondary metabolites, endomeketals A–B (1–2), a new natural product (3), and a known compound (4) were isolated from the ethyl acetate extract of the endophytic fungus Endomelanconiopsis endophytica A326 derived from Ficus hirta. Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. However, no compound showed cytotoxic activity against these human tumor cell lines. Full article

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4529 KiB

Open AccessArticle

Photoelectrochemical Behavior of Electrophoretically Deposited Hematite Thin Films Modified with Ti(IV)

by Nicola Dalle Carbonare, Rita Boaretto, Stefano Caramori, Roberto Argazzi, Maurizio Dal Colle, Luca Pasquini, Renzo Bertoncello, Marcello Marelli, Claudio Evangelisti and Carlo Alberto Bignozzi

Molecules 2016, 21(7), 942; https://doi.org/10.3390/molecules21070942 - 20 Jul 2016

Cited by 6 | Viewed by 5974

Abstract

Doping hematite with different elements is a common strategy to improve the electrocatalytic activity towards the water oxidation reaction, although the exact effect of these external agents is not yet clearly understood. Using a feasible electrophoretic procedure, we prepared modified hematite films by [...] Read more.

Doping hematite with different elements is a common strategy to improve the electrocatalytic activity towards the water oxidation reaction, although the exact effect of these external agents is not yet clearly understood. Using a feasible electrophoretic procedure, we prepared modified hematite films by introducing in the deposition solution Ti(IV) butoxide. Photoelectrochemical performances of all the modified electrodes were superior to the unmodified one, with a 4-fold increase in the photocurrent at 0.65 V vs. SCE in 0.1 M NaOH (pH 13.3) for the 5% Ti-modified electrode, which was the best performing electrode. Subsequent functionalization with an iron-based catalyst led, at the same potential, to a photocurrent of ca. 1.5 mA·cm⁻², one of the highest achieved with materials based on solution processing in the absence of precious elements. AFM, XPS, TEM and XANES analyses revealed the formation of different Ti(IV) oxide phases on the hematite surface, that can reduce surface state recombination and enhance hole injection through local surface field effects, as confirmed by electrochemical impedance analysis. Full article

(This article belongs to the Special Issue Photocatalytic Water Splitting—the Untamed Dream)

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3331 KiB

Open AccessArticle

Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2–Inhibitory Activities from Marine-Derived Fungus Aspergillus niger

by Wei Fang, Xiuping Lin, Jianjiao Wang, Yonghong Liu, Huaming Tao and Xuefeng Zhou

Molecules 2016, 21(7), 941; https://doi.org/10.3390/molecules21070941 - 20 Jul 2016

Cited by 23 | Viewed by 7101

Abstract

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and [...] Read more.

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC₅₀ > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2–inhibitory activities, with the IC₅₀ values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2–inhibitory activities of BNPs have been reported. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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388 KiB

Open AccessArticle

Structures and Biogenesis of Fallaxosides D₄, D₅, D₆ and D₇, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

by Alexandra S. Silchenko, Anatoly I. Kalinovsky, Sergey A. Avilov, Pelageya V. Andryjaschenko, Pavel S. Dmitrenok, Vladimir I. Kalinin, Ekaterina A. Chingizova, Kirill V. Minin and Valentin A. Stonik

Molecules 2016, 21(7), 939; https://doi.org/10.3390/molecules21070939 - 20 Jul 2016

Cited by 14 | Viewed by 5174

Abstract

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides [...] Read more.

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8)-, 8(9)- or 9(11)-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1–4 have three sulfate groups. The cytotoxic activity of glycosides 1–4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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243 KiB

Open AccessReview

Bioactivities and Health Benefits of Mushrooms Mainly from China

by Jiao-Jiao Zhang, Ya Li, Tong Zhou, Dong-Ping Xu, Pei Zhang, Sha Li and Hua-Bin Li

Molecules 2016, 21(7), 938; https://doi.org/10.3390/molecules21070938 - 20 Jul 2016

Cited by 120 | Viewed by 19146

Abstract

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing [...] Read more.

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing attention in recent years, and could be developed into functional food or medicines for prevention and treatment of several chronic diseases, such as cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases. The present review summarizes the bioactivities and health benefits of mushrooms, and could be useful for full utilization of mushrooms. Full article

(This article belongs to the Section Natural Products Chemistry)

5183 KiB

Open AccessReview

A Novel Strategy for Biomass Upgrade: Cascade Approach to the Synthesis of Useful Compounds via C-C Bond Formation Using Biomass-Derived Sugars as Carbon Nucleophiles

by Sho Yamaguchi and Toshihide Baba

Molecules 2016, 21(7), 937; https://doi.org/10.3390/molecules21070937 - 20 Jul 2016

Cited by 20 | Viewed by 8288

Abstract

Due to the depletion of fossil fuels, biomass-derived sugars have attracted increasing attention in recent years as an alternative carbon source. Although significant advances have been reported in the development of catalysts for the conversion of carbohydrates into key chemicals (e.g., degradation approaches [...] Read more.

Due to the depletion of fossil fuels, biomass-derived sugars have attracted increasing attention in recent years as an alternative carbon source. Although significant advances have been reported in the development of catalysts for the conversion of carbohydrates into key chemicals (e.g., degradation approaches based on the dehydration of hydroxyl groups or cleavage of C-C bonds via retro-aldol reactions), only a limited range of products can be obtained through such processes. Thus, the development of a novel and efficient strategy targeted towards the preparation of a range of compounds from biomass-derived sugars is required. We herein describe the highly-selective cascade syntheses of a range of useful compounds using biomass-derived sugars as carbon nucleophiles. We focus on the upgrade of C2 and C3 oxygenates generated from glucose to yield useful compounds via C-C bond formation. The establishment of this novel synthetic methodology to generate valuable chemical products from monosaccharides and their decomposed oxygenated materials renders carbohydrates a potential alternative carbon resource to fossil fuels. Full article

(This article belongs to the Special Issue Cascade Catalysis)

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863 KiB

Open AccessArticle

Synthesis, Spectral Characterization of Several Novel Pyrene-Derived Aminophosphonates and Their Ecotoxicological Evaluation Using Heterocypris incongruens and Vibrio fisheri Tests

by Jarosław Lewkowski, Maria Rodriguez Moya, Marta Chmielak, Diana Rogacz, Kamila Lewicka and Piotr Rychter

Molecules 2016, 21(7), 936; https://doi.org/10.3390/molecules21070936 - 19 Jul 2016

Cited by 12 | Viewed by 5923

Abstract

Four diphenyl pyrene-derived aminophosphonates were synthesized. Attempts were made to synthesize diphenyl N-(R)-α-methylbenzylamino(pyren-1-yl)methylphosphonate (3e) in order to obtain the chiral aminophosphonate bearing a pyrene moiety. Because these attempts failed, dimethyl and dibenzyl N-(R)-α-methylbenzyl substituted aminophosphonates [...] Read more.

Four diphenyl pyrene-derived aminophosphonates were synthesized. Attempts were made to synthesize diphenyl N-(R)-α-methylbenzylamino(pyren-1-yl)methylphosphonate (3e) in order to obtain the chiral aminophosphonate bearing a pyrene moiety. Because these attempts failed, dimethyl and dibenzyl N-(R)-α-methylbenzyl substituted aminophosphonates 4 and 5 were synthesized and the predominant diastereoisomer of dimethyl aminophosphonate 4 was isolated. The resolution of the diastereomeric mixture of 5 failed. Aminophosphonates 3a–d and the predominant diastereoisomer of 4 were investigated in terms of their ecotoxicity using tests performed on the ostracode Heterocypris incongruens and the fluorescent bacterium Vibrio fisheri. The tests confirmed the moderate-to-high ecotoxicity of aminophosphonates 3a–d and 4, but no evident correlation between the structure and toxicity has been found. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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2934 KiB

Open AccessArticle

Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27^KIP1-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells

by Shi Zhong, You-Gui Li, Dong-Feng Ji, Tian-Bao Lin and Zhi-Qiang Lv

Molecules 2016, 21(7), 934; https://doi.org/10.3390/molecules21070934 - 19 Jul 2016

Cited by 29 | Viewed by 7143

Abstract

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA [...] Read more.

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner. Western blot results showed that PCA treatment decreased the expression levels of cyclin A, cyclin D1, and p27^KIP1 but increased those of cyclin-dependent kinase 2 (CDK2) in HT-29 cells. Furthermore, the expression levels of B-cell lymphoma/leukemia-2 (Bcl-2) and B-cell lymphoma/leukemia-xL (Bcl-xL) were down-regulated, whereas the levels of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak), and cytosolic cytochrome c were significantly upregulated. Thus, the enzymes caspases-9, -3, -8, and -6 were found to be activated in HT-29 cells with PCA treatment. These results indicate that PCA-induced S-phase cell cycle arrest and apoptosis involve p27^KIP1-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway. Full article

(This article belongs to the Section Natural Products Chemistry)

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