Molecules

322 KiB

Open AccessArticle

Two Ellagic Acids Isolated from Roots of Sanguisorba officinalis L. Promote Hematopoietic Progenitor Cell Proliferation and Megakaryocyte Differentiation

by Xiaoping Gao, Jianming Wu, Wenjun Zou and Yanping Dai

Molecules 2014, 19(4), 5448-5458; https://doi.org/10.3390/molecules19045448 - 24 Apr 2014

Cited by 37 | Viewed by 7298

Abstract

Using a bioassay-directed chromatographic separation, two ellagic acids were obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis L. On the basis of chemical and spectroscopic methods, the two ellagic acids were identified as 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside [...] Read more.

Using a bioassay-directed chromatographic separation, two ellagic acids were obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis L. On the basis of chemical and spectroscopic methods, the two ellagic acids were identified as 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside and 3,3',4-tri-O-methylellagic acid. Stimulation of cell proliferation was assayed in hematopoietic progenitor cells using the Cell Counting kit-8 method. The megakaryocyte differentiation was determined in human erythroleukemia (HEL) cells using Giemsa staining and flow cytometry analysis. The ellagic acids significantly stimulated the proliferation of Baf3/Mpl cells. Morphology analysis and megakaryocyte specific-marker CD41 staining confirmed that the ellagic acids induced megakaryocyte differentiation in HEL cells. This is the first time that 3,3',4-tri-O-methylellagic acid or 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside are reported to induce megakaryopoiesis, suggesting a class of small molecules which differ from others non-peptidyl, and appears to have potential for clinical development as a therapeutic agent for patients with blood platelet disorders. Full article

(This article belongs to the Section Natural Products Chemistry)

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287 KiB

Open AccessArticle

Quantification, Antioxidant and Antimicrobial Activity of Phenolics Isolated from Different Extracts of Capsicum frutescens (Pimenta Malagueta)

by Patrícia L. A. Nascimento, Talita C. E. S. Nascimento, Natália S. M. Ramos, Girliane R. Silva, José Erick Galindo Gomes, Rosângela E. A. Falcão, Keila A. Moreira, Ana L. F. Porto and Tania M. S. Silva

Molecules 2014, 19(4), 5434-5447; https://doi.org/10.3390/molecules19045434 - 24 Apr 2014

Cited by 102 | Viewed by 13656

Abstract

This paper presents the quantification, antioxidant and antimicrobial activity of capsaicin, dihydrocapsaicin and the flavonoid chrysoeriol isolated from different extracts (hexane and acetonitrile extracts from whole fruit, peel and seed) of Capsicum frutescens (pimenta malagueta). The acetonitrile extract of the seeds, peel and [...] Read more.

This paper presents the quantification, antioxidant and antimicrobial activity of capsaicin, dihydrocapsaicin and the flavonoid chrysoeriol isolated from different extracts (hexane and acetonitrile extracts from whole fruit, peel and seed) of Capsicum frutescens (pimenta malagueta). The acetonitrile extract of the seeds, peel and whole fruits contained capsaicin as a major component, followed in abundance by dihydrocapsaicin and chrysoeriol. The antimicrobial activity of the isolated compounds against seven microorganisms showed chrysoeriol was the most active compound. In the antioxidant test, the acetonitrile extract from the whole fruit showed the highest activity. The antioxidant activity of pimenta malagueta may be correlated with its phenolic content, principally with the most active compound, capsaicin. Full article

(This article belongs to the Section Natural Products Chemistry)

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1346 KiB

Open AccessArticle

Conformational Characterization of Ipomotaosides and Their Recognition by COX-1 and 2

by Pablo R. Arantes, Liana G. Sachett, Cedric S. Graebin and Hugo Verli

Molecules 2014, 19(4), 5421-5433; https://doi.org/10.3390/molecules19045421 - 24 Apr 2014

Cited by 5 | Viewed by 5997

Abstract

The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be [...] Read more.

The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility. In this context, the current work presents a conformational characterization of ipomotaosides A–D in aqueous and nonaqueous solvents. The employed protocol includes metadynamics evaluation and unrestrained molecular dynamics simulations (MD). The obtained data provided structural models for the ipomotaosides in good agreement with previous ROESY distances measured in pyridine. Accordingly, the most abundant conformation of ipomotaoside A in solution was employed in flexible docking studies, providing a structural basis for the compound’s inhibition of COX enzymes. The so-obtained complex supports resin glycosides’ role as original scaffolds for future studies, aiming at structural optimization and development of potential new anti-inflammatory agents. Full article

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

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408 KiB

Open AccessArticle

In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens

by Claudio L. Donnici, Luciano J. Nogueira, Maria Helena Araujo, Sheila Rodrigues Oliveira, Thais F. F. Magalhães, Miriam T. P. Lopes, Ana Cândida Araújo e Silva, Ana Maria da Costa Ferreira, Cleide V. B. Martins and Maria A. De Resende Stoianoff

Molecules 2014, 19(4), 5402-5420; https://doi.org/10.3390/molecules19045402 - 24 Apr 2014

Cited by 12 | Viewed by 7517

Abstract

The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical [...] Read more.

The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10⁻⁶ mol mL⁻¹ to 10⁻⁸ mol mL⁻¹) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC₅₀) showed that the complexes are not as toxic (IC₅₀ values are much higher—30 to 200 fold—than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs). Full article

(This article belongs to the Special Issue Ruthenium Complex)

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293 KiB

Open AccessReview

Role of MicroRNA in Response to Ionizing Radiations: Evidences and Potential Impact on Clinical Practice for Radiotherapy

by Francesco Cellini, Alessio G. Morganti, Domenico Genovesi, Nicola Silvestris and Vincenzo Valentini

Molecules 2014, 19(4), 5379-5401; https://doi.org/10.3390/molecules19045379 - 24 Apr 2014

Cited by 61 | Viewed by 8655

Abstract

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in [...] Read more.

MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments—they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest. Full article

(This article belongs to the Special Issue miRNAs as Probes to Monitor Cancer and Neurodegenerative Disorders)

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Open AccessArticle

Antioxidant and Antiproliferative Activities of Methanolic Extract from a Neglected Agricultural Product: Corn Cobs

by Raniere Fagundes Melo-Silveira, Gabriel Pereira Fidelis, Rony Lucas Silva Viana, Vinícius Campelo Soeiro, Rodrigo Augusto da Silva, Daisy Machado, Leandro Silva Costa, Carmen Veríssima Ferreira and Hugo Alexandre Oliveira Rocha

Molecules 2014, 19(4), 5360-5378; https://doi.org/10.3390/molecules19045360 - 24 Apr 2014

Cited by 31 | Viewed by 8036

Abstract

Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro [...] Read more.

Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl₄. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity. Full article

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Open AccessArticle

Effect of High Pressure Microfluidization on the Crystallization Behavior of Palm Stearin — Palm Olein Blends

by Lijuan Han, Lin Li, Bing Li, Lei Zhao, Guoqin Liu, Xinqi Liu and Xuede Wang

Molecules 2014, 19(4), 5348-5359; https://doi.org/10.3390/molecules19045348 - 24 Apr 2014

Cited by 10 | Viewed by 7429

Abstract

Moderate and high microfluidization pressures (60 and 120 MPa) and different treatment times (once and twice) were used to investigate the effect of high-pressure microfluidization (HPM) treatment on the crystallization behavior and physical properties of binary mixtures of palm stearin (PS) and palm [...] Read more.

Moderate and high microfluidization pressures (60 and 120 MPa) and different treatment times (once and twice) were used to investigate the effect of high-pressure microfluidization (HPM) treatment on the crystallization behavior and physical properties of binary mixtures of palm stearin (PS) and palm olein (PO). The polarized light microscopy (PLM), texture analyzer, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) techniques were applied to analyze the changes in crystal network structure, hardness, polymorphism and thermal property of the control and treated blends. PLM results showed that HPM caused significant reductions in maximum crystal diameter in all treated blends, and thus led to changes in the crystal network structure, and finally caused higher hardness in than the control blends. The XRD study demonstrated that HPM altered crystalline polymorphism. The HPM-treated blends showed a predominance of the more stable β' form, which is of more interest for food applications, while the control blend had more α- and β-form. This result was further confirmed by DSC observations. These changes in crystallization behavior indicated that HPM treatment was more likely to modify the crystallization processes and nucleation mechanisms. Full article

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Open AccessArticle

Rice Bran Feruloylated Oligosaccharides Activate Dendritic Cells via Toll-Like Receptor 2 and 4 Signaling

by Chi Chen Lin, Hua Han Chen, Yu Kuo Chen, Hung Chia Chang, Ping Yi Lin, I-Hong Pan, Der-Yuan Chen, Chuan Mu Chen and Su Yi Lin

Molecules 2014, 19(4), 5325-5347; https://doi.org/10.3390/molecules19045325 - 23 Apr 2014

Cited by 24 | Viewed by 7329

Abstract

This work presents the effects of feruloylated oligosaccharides (FOs) of rice bran on murine bone marrow-derived dendritic cells (BMDCs) and the potential pathway through which the effects are mediated. We found that FOs induced phenotypic maturation of DCs, as shown by the increased [...] Read more.

This work presents the effects of feruloylated oligosaccharides (FOs) of rice bran on murine bone marrow-derived dendritic cells (BMDCs) and the potential pathway through which the effects are mediated. We found that FOs induced phenotypic maturation of DCs, as shown by the increased expression of CD40, CD80/CD86 and MHC-I/II molecules. FOs efficiently induced maturation of DCs generated from C3H/HeN or C57BL/6 mice with normal toll-like receptor 4 (TLR-4) or TLR-2 but not DCs from mice with mutated TLR4 or TLR2. The mechanism of action of FOs may be mediated by increased phosphorylation of ERK, p38 and JNK mitogen-activated protein kinase (MAPKs) and increased NF-kB activity, which are important signaling molecules downstream of TLR-4 and TLR-2. These data suggest that FOs induce DCs maturation through TLR-4 and/or TLR-2 and that FOs might have potential efficacy against tumor or virus infection or represent a candidate-adjuvant approach for application in immunotherapy and vaccination. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis, Crystal Structure, Spectra and Quantum Chemical Study on 1-Phenyl-3-(4-nitrophenyl)-5-(2-thienyl)-2-pyrazoline

by Huan-Mei Guo, Pu-Su Zhao, Qian Wu and Yu-Feng Li

Molecules 2014, 19(4), 5313-5324; https://doi.org/10.3390/molecules19045313 - 23 Apr 2014

Cited by 1 | Viewed by 6495

Abstract

1-Phenyl-3-(4-nitrophenyl)-5-(2-thienyl)-2-pyrazoline was synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction. UV-Vis spectra and fluorescence spectra were measured. Density functional theory calculations on the structure of the title compound were performed at the B3LYP/6-311G** level of theory. NPA atomic charge [...] Read more.

1-Phenyl-3-(4-nitrophenyl)-5-(2-thienyl)-2-pyrazoline was synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction. UV-Vis spectra and fluorescence spectra were measured. Density functional theory calculations on the structure of the title compound were performed at the B3LYP/6-311G** level of theory. NPA atomic charge distributions indicate that, although the S atom in the thienyl ring loses coordination capacity, the title compound still may be used as a potential multi-dentate ligand to coordinate with metallic ions. The calculation of the second order optical nonlinearity was carried out. Natural bond orbital analyses indicate that the electronic absorption bands are mainly derived from the contribution of n → π* and π → π* transitions. Fluorescence spectra determination shows that the title compound is a potential orange-light emitting material. Full article

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632 KiB

Open AccessArticle

Identifying Stereoisomers by ab-initio Calculation of Secondary Isotope Shifts on NMR Chemical Shieldings

by Karl-Heinz Böhm, Klaus Banert and Alexander A. Auer

Molecules 2014, 19(4), 5301-5312; https://doi.org/10.3390/molecules19045301 - 23 Apr 2014

Cited by 3 | Viewed by 6334

Abstract

We present ab-initio calculations of secondary isotope effects on NMR chemical shieldings. The change of the NMR chemical shift of a certain nucleus that is observed if another nucleus is replaced by a different isotope can be calculated by computing vibrational corrections on [...] Read more.

We present ab-initio calculations of secondary isotope effects on NMR chemical shieldings. The change of the NMR chemical shift of a certain nucleus that is observed if another nucleus is replaced by a different isotope can be calculated by computing vibrational corrections on the NMR parameters using electronic structure methods. We demonstrate that the accuracy of the computational results is sufficient to even distinguish different conformers. For this purpose, benchmark calculations for fluoro(2-2H)ethane in gauche and antiperiplanar conformation are carried out at the HF, MP2 and CCSD(T) level of theory using basis sets ranging from double- to quadruple-zeta quality. The methodology is applied to the secondary isotope shifts for 2-fluoronorbornane in order to resolve an ambiguity in the literature on the assignment of endo- and exo-2-fluoronorbornanes with deuterium substituents in endo-3 and exo-3 positions, also yielding insight into mechanistic details of the corresponding synthesis. Full article

(This article belongs to the Collection Isotope Effects)

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Open AccessArticle

Thermodynamics and Kinetics of Guest-Induced Switching between “Basket Handle” Porphyrin Isomers

by Alexander B. C. Deutman, Tim Woltinge, Jan M. M. Smits, René De Gelder, Johannes A. A. W. Elemans, Roeland J. M. Nolte and Alan E. Rowan

Molecules 2014, 19(4), 5278-5300; https://doi.org/10.3390/molecules19045278 - 23 Apr 2014

Cited by 6 | Viewed by 8123

Abstract

The synthesis and switching properties of two “basket handle” porphyrin isomers is described. The cis-oriented meso-phenyl groups of these porphyrins are linked at their ortho-positons via benzocrown-ether-based spacers, which as a result of slow atropisomerization are located either on the [...] Read more.

The synthesis and switching properties of two “basket handle” porphyrin isomers is described. The cis-oriented meso-phenyl groups of these porphyrins are linked at their ortho-positons via benzocrown-ether-based spacers, which as a result of slow atropisomerization are located either on the same side of the porphyrin plane (cis), or on opposite sides (trans). In solution, the cis-linked isomer slowly isomerizes in the direction of the thermodynamically more stable trans-isomer. In the presence of viologen (N,N'-dialkyl-4,4'-bipyridinium) derivatives, which have different affinities for the two isomers, the isomerization equilibrium could be significantly influenced. In addition, the presence of these guests was found to enhance the rate of the switching process, which was suggested to be caused by favorable interactions between the positively charged guest and the crown ethers of the receptor, stabilizing the transition state energies of the isomerization reaction between the two isomers. Full article

(This article belongs to the Special Issue Molecular Switches)

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333 KiB

Open AccessArticle

Immunostimulatory Effects of Polysaccharides Isolated from Makgeolli (Traditional Korean Rice Wine)

by Chang-Won Cho, Chun-ji Han, Young Kyoung Rhee, Young-Chul Lee, Kwang-Soon Shin and Hee-Do Hong

Molecules 2014, 19(4), 5266-5277; https://doi.org/10.3390/molecules19045266 - 23 Apr 2014

Cited by 23 | Viewed by 6633

Abstract

Makgeolli is a traditional Korean rice wine, reported to have various biological functions. In this study, the immunostimulatory activity of a polysaccharide from makgeolli (PSM) was investigated. The polysaccharide fraction was isolated from makgeolli by hot water extraction, ethanol precipitation, dialysis, and lyophilization. [...] Read more.

Makgeolli is a traditional Korean rice wine, reported to have various biological functions. In this study, the immunostimulatory activity of a polysaccharide from makgeolli (PSM) was investigated. The polysaccharide fraction was isolated from makgeolli by hot water extraction, ethanol precipitation, dialysis, and lyophilization. The major constituents in PSM were neutral sugars (87.3%). PSM was composed of five different sugars, glucose, mannose, galactose, xylose, and arabinose. In normal mice, PSM treatment increased the spleen index (p < 0.05) as well as splenocyte proliferation (p < 0.05) in combination with concanavalin A or lipopolysaccharide. The immunostimulatory activities of PSM were also examined in cyclophosphamide (CY)-induced immunosuppressed mice. Mice treated with PSM exhibited increased splenocyte proliferation (p < 0.05), natural killer cell activity, and white blood cell counts (p < 0.01) compared with immunosuppressed mice. These results indicate that PSM can enhance immune function in normal mice and CY-induced immunosuppressed mice. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Integrated Computational Tools for Identification of CCR5 Antagonists as Potential HIV-1 Entry Inhibitors: Homology Modeling, Virtual Screening, Molecular Dynamics Simulations and 3D QSAR Analysis

by Suri Moonsamy, Radha Charan Dash and Mahmoud E. S. Soliman

Molecules 2014, 19(4), 5243-5265; https://doi.org/10.3390/molecules19045243 - 23 Apr 2014

Cited by 15 | Viewed by 8970

Abstract

Using integrated in-silico computational techniques, including homology modeling, structure-based and pharmacophore-based virtual screening, molecular dynamic simulations, per-residue energy decomposition analysis and atom-based 3D-QSAR analysis, we proposed ten novel compounds as potential CCR5-dependent HIV-1 entry inhibitors. Via validated docking calculations, binding free energies revealed [...] Read more.

Using integrated in-silico computational techniques, including homology modeling, structure-based and pharmacophore-based virtual screening, molecular dynamic simulations, per-residue energy decomposition analysis and atom-based 3D-QSAR analysis, we proposed ten novel compounds as potential CCR5-dependent HIV-1 entry inhibitors. Via validated docking calculations, binding free energies revealed that novel leads demonstrated better binding affinities with CCR5 compared to maraviroc, an FDA-approved HIV-1 entry inhibitor and in clinical use. Per-residue interaction energy decomposition analysis on the averaged MD structure showed that hydrophobic active residues Trp86, Tyr89 and Tyr108 contributed the most to inhibitor binding. The validated 3D-QSAR model showed a high cross-validated r_cv² value of 0.84 using three principal components and non-cross-validated r² value of 0.941. It was also revealed that almost all compounds in the test set and training set yielded a good predicted value. Information gained from this study could shed light on the activity of a new series of lead compounds as potential HIV entry inhibitors and serve as a powerful tool in the drug design and development machinery. Full article

(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)

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Open AccessArticle

The Intramolecular Diels-Alder Reaction of Diarylheptanoids — Quantum Chemical Calculation of Structural Features Favoring the Formation of Phenylphenalenones

by Yulia Monakhova and Bernd Schneider

Molecules 2014, 19(4), 5231-5242; https://doi.org/10.3390/molecules19045231 - 23 Apr 2014

Cited by 6 | Viewed by 6275

Abstract

Diarylheptanoids have been reported as biosynthetic precursors of phenylphenalenones in plants. Quantum chemical calculations of molecular geometry and orbitals were used to elaborate which structural features are required to determine if diarylheptanoids can undergo an intramolecular Diel-Alder reaction to form phenylphenalenones. The computational [...] Read more.

Diarylheptanoids have been reported as biosynthetic precursors of phenylphenalenones in plants. Quantum chemical calculations of molecular geometry and orbitals were used to elaborate which structural features are required to determine if diarylheptanoids can undergo an intramolecular Diel-Alder reaction to form phenylphenalenones. The computational data showed that an ortho-quinone- or a hydoxyketone-bearing ring A, containing the dienophile moiety, and a heptadiene chain with conjugated cisoid double bonds at C-4/C-6 and a saturated segment consisting of two sp³-carbon atoms, are required. Only four diarylheptanoids out of eighteen studied compounds proved to be suitable candidates. Among them are two 3,5-dideoxy compounds and two other compounds oxygenated only at C-3, suggesting that lachnanthocarpone, a representative of the 6-oxygenated phenylphenalenones, and anigorufone, a representative of the 6-deoxy phenylphenalenones, are not connected via a precursor-product relationship (“late reduction at C-6”) but formed through partially separate pathways. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Bioactivity of a Family of Chiral Nonracemic Aminobenzylnaphthols towards Candida albicans

by Maria Annunziata M. Capozzi, Cosimo Cardellicchio, Angela Magaletti, Antonio Bevilacqua, Marianne Perricone and Maria Rosaria Corbo

Molecules 2014, 19(4), 5219-5230; https://doi.org/10.3390/molecules19045219 - 23 Apr 2014

Cited by 12 | Viewed by 5319

Abstract

Chiral nonracemic aminobenzylnaphthols were obtained by a Betti multi-component reaction between 2-naphthol, aryl aldehydes and enantiopure arylethylamine. Moreover, some new aminobenzylnaphthols were synthesized by a similar reaction between 2-naphthol, aryl aldehydes and prolinol. These aminobenzylnaphthols, synthesized from different components and thus having different [...] Read more.

Chiral nonracemic aminobenzylnaphthols were obtained by a Betti multi-component reaction between 2-naphthol, aryl aldehydes and enantiopure arylethylamine. Moreover, some new aminobenzylnaphthols were synthesized by a similar reaction between 2-naphthol, aryl aldehydes and prolinol. These aminobenzylnaphthols, synthesized from different components and thus having different structural features, were tested as anti-yeast agents inhibiting Candida albicans. The effect towards the test strain was studied with a microdilution approach and three different concentrations (150, 300 and 450 µg/mL) were tested. The best results were found for the aminobenzylnaphthols obtained from 1-naphthylethylamine and from natural prolinol. The use of the two-way ANOVA highlighted the better performances of the prolinol derivative among the differently structured aminobenzylnaphthols that were screened. The activity towards C. albicans of this prolinol derivative resulted to be interesting and could represent a promising alternative to overcome the problem of the strains resistant to the traditional antifungals. Full article

(This article belongs to the Special Issue Parallel Synthesis)

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Open AccessArticle

A Benzoic Acid Derivative and Flavokawains from Piper species as Schistosomiasis Vector Controls

by Ludmila N. Rapado, Giovana C. Freitas, Adriano Polpo, Maritza Rojas-Cardozo, Javier V. Rincón, Marcus T. Scotti, Massuo J. Kato, Eliana Nakano and Lydia F. Yamaguchi

Molecules 2014, 19(4), 5205-5218; https://doi.org/10.3390/molecules19045205 - 23 Apr 2014

Cited by 11 | Viewed by 7377

Abstract

The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic [...] Read more.

The search of alternative compounds to control tropical diseases such as schistosomiasis has pointed to secondary metabolites derived from natural sources. Piper species are candidates in strategies to control the transmission of schistosomiasis due to their production of molluscicidal compounds. A new benzoic acid derivative and three flavokawains from Piper diospyrifolium, P. cumanense and P. gaudichaudianum displayed significant activities against Biomphalaria glabrata snails. Additionally, “in silico” studies were performed using docking assays and Molecular Interaction Fields to evaluate the physical-chemical differences among the compounds in order to characterize the observed activities of the test compounds against Biomphalaria glabrata snails. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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Open AccessArticle

Anti-Amoebic Properties of Carbonyl Thiourea Derivatives

by Maizatul Akma Ibrahim, Mohd Sukeri Mohd Yusof and Nakisah Mat Amin

Molecules 2014, 19(4), 5191-5204; https://doi.org/10.3390/molecules19045191 - 22 Apr 2014

Cited by 22 | Viewed by 7489

Abstract

Thiourea derivatives display a broad spectrum of applications in chemistry, various industries, medicines and various other fields. Recently, different thiourea derivatives have been synthesized and explored for their anti-microbial properties. In this study, four carbonyl thiourea derivatives were synthesized and characterized, and then [...] Read more.

Thiourea derivatives display a broad spectrum of applications in chemistry, various industries, medicines and various other fields. Recently, different thiourea derivatives have been synthesized and explored for their anti-microbial properties. In this study, four carbonyl thiourea derivatives were synthesized and characterized, and then further tested for their anti-amoebic properties on two potential pathogenic species of Acanthamoeba, namely A. castellanii (CCAP 1501/2A) and A. polyphaga (CCAP 1501/3A). The results indicate that these newly-synthesized thiourea derivatives are active against both Acanthamoeba species. The IC₅₀ values obtained were in the range of 2.39–8.77 µg·mL^‑1 (9.47–30.46 µM) for A. castellanii and 3.74–9.30 µg·mL^‑1 (14.84–31.91 µM) for A. polyphaga. Observations on the amoeba morphology indicated that the compounds caused the reduction of the amoeba size, shortening of their acanthopodia structures, and gave no distinct vacuolar and nuclear structures in the amoeba cells. Meanwhile, fluorescence microscopic observation using acridine orange and propidium iodide (AOPI) staining revealed that the synthesized compounds induced compromised-membrane in the amoeba cells. The results of this study proved that these new carbonyl thiourea derivatives, especially compounds M1 and M2 provide potent cytotoxic properties toward pathogenic Acanthamoeba to suggest that they can be developed as new anti-amoebic agents for the treatment of Acanthamoeba keratitis. Full article

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Open AccessArticle

Antioxidant and Antitumor Activities of New Synthesized Aromatic C-Nucleoside Derivatives

by Mohamed M. El Sadek, Nagwa S. Abd El-Dayem, Seham Y. Hassan, Mohamed A. Mostafa and Galila A. Yacout

Molecules 2014, 19(4), 5163-5190; https://doi.org/10.3390/molecules19045163 - 22 Apr 2014

Cited by 12 | Viewed by 6162

Abstract

The carbohydrazide 1 was used as the precursor for the synthesis of a number of new aromatic C-nucleosides containing 1,3,4-oxadiazole 7, [1,3,4]oxadiazolo[2,3-a]isoindole 10b and pyrazole units 18. On the other hand, the thiosemicarbazone 20 was used as the key intermediate [...] Read more.

The carbohydrazide 1 was used as the precursor for the synthesis of a number of new aromatic C-nucleosides containing 1,3,4-oxadiazole 7, [1,3,4]oxadiazolo[2,3-a]isoindole 10b and pyrazole units 18. On the other hand, the thiosemicarbazone 20 was used as the key intermediate for synthesis of 1,3,4-oxadiazole and 1,2,4-triazole-3-thione derivatives 21 and 23. The antioxidant activities of the prepared compounds were evaluated. The carbohydrazide 1 in particular was found to have potent antioxidant and antitumor activity. Full article

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Open AccessArticle

Development of Simple Sequence Repeat (SSR) Markers of Sesame (Sesamum indicum) from a Genome Survey

by Xin Wei, Linhai Wang, Yanxin Zhang, Xiaoqiong Qi, Xiaoling Wang, Xia Ding, Jing Zhang and Xiurong Zhang

Molecules 2014, 19(4), 5150-5162; https://doi.org/10.3390/molecules19045150 - 22 Apr 2014

Cited by 67 | Viewed by 9645

Abstract

Sesame (Sesamum indicum), an important oil crop, is widely grown in tropical and subtropical regions. It provides part of the daily edible oil allowance for almost half of the world’s population. A limited number of co-dominant markers has been developed and [...] Read more.

Sesame (Sesamum indicum), an important oil crop, is widely grown in tropical and subtropical regions. It provides part of the daily edible oil allowance for almost half of the world’s population. A limited number of co-dominant markers has been developed and applied in sesame genetic diversity and germplasm identity studies. Here we report for the first time a whole genome survey used to develop simple sequence repeat (SSR) markers and to detect the genetic diversity of sesame germplasm. From the initial assembled sesame genome, 23,438 SSRs (≥5 repeats) were identified. The most common repeat motif was dinucleotide with a frequency of 84.24%, followed by 13.53% trinucleotide, 1.65% tetranucleotide, 0.3% pentanucleotide and 0.28% hexanucleotide motifs. From 1500 designed and synthesised primer pairs, 218 polymorphic SSRs were developed and used to screen 31 sesame accessions that from 12 countries. STRUCTURE and phylogenetic analyses indicated that all sesame accessions could be divided into two groups: one mainly from China and another from other countries. Cluster analysis classified Chinese major sesame varieties into three groups. These novel SSR markers are a useful tool for genetic linkage map construction, genetic diversity detection, and marker-assisted selective sesame breeding. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells

by Kyung Hoon Oh, Yoonjin Nam, Ji Hoon Jeong, In Kyeom Kim and Uy Dong Sohn

Molecules 2014, 19(4), 5135-5149; https://doi.org/10.3390/molecules19045135 - 22 Apr 2014

Cited by 12 | Viewed by 6214

Abstract

Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter found in blood platelets, the gastrointestinal (GI) tract, and the central nervous system (CNS) of animals and humans. The signaling pathways of 5-hydroxytryptamine (5-HT)-induced contractions in cat esophageal smooth muscle cell (ESMC)s have been identified, [...] Read more.

Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter found in blood platelets, the gastrointestinal (GI) tract, and the central nervous system (CNS) of animals and humans. The signaling pathways of 5-hydroxytryptamine (5-HT)-induced contractions in cat esophageal smooth muscle cell (ESMC)s have been identified, but the downstream components of the 5-HT signaling pathway remain unclear. DA-9701 is the standardized extract of the Pharbitis nil Choisy seed (Pharbitidis Semen, Convolvulaceae) and the root of Corydalis yahusuo W.T. Wang (Corydalis Tuber, Papaveraceae). DA-9701 is known to have strong gastroprokinetic effects and a good safety profile. In this study, we investigated the 5-HT signaling pathway at the G-protein level, and we explored the mechanisms by which DA-9701 induces smooth muscle contraction. Freshly isolated smooth muscle cells were harvested from the feline esophagus, and cells were permeabilized to measure their length. 5-HT produced esophageal smooth muscle contractions in a dose-dependent manner. Furthermore, 5-HT produced a relatively long-acting contraction. 5-HT binds to the 5-HT₂, 5-HT₃ and 5-HT₄ receptors to induce smooth muscle contraction in feline ESMCs. These receptors, which are located in esophageal smooth muscle, are coupled to G_αq, G_αo and G_αs. These G proteins activate PLC, which leads to Ca²⁺/calmodulin-dependent MLCK activation, resulting in MLC₂₀ phosphorylation and cell contraction. Conversely, DA-9701 inhibits 5-HT-induced contraction by inhibiting MLC₂₀ phosphorylation. Full article

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Open AccessArticle

Catechins and Procyanidins of Ginkgo biloba Show Potent Activities towards the Inhibition of β-Amyloid Peptide Aggregation and Destabilization of Preformed Fibrils

by Haiyan Xie, Jing-Rong Wang, Lee-Fong Yau, Yong Liu, Liang Liu, Quan-Bin Han, Zhongzhen Zhao and Zhi-Hong Jiang

Molecules 2014, 19(4), 5119-5134; https://doi.org/10.3390/molecules19045119 - 22 Apr 2014

Cited by 45 | Viewed by 7851

Abstract

Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761). In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and [...] Read more.

Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761). In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with reference compounds, six of them were identified as (+)-catechin, (−)-epicatechin, (−)-gallocatechin, (−)-epigallocatechin and procyanidins B₁ and B₃. The activities of these polyphenols in the inhibition of Aβ42 aggregation and the destabilization of preformed fibrils were evaluated using biochemical assays, which showed that all six of the polyphenols, as well as a fraction of the extract of Ginkgo biloba leaves (EGb) containing catechins and procyanidins, exerted potent inhibitory activities towards Aβ42 aggregation and could also destabilize the performed fibrils. Catechins and procyanidins can therefore be regarded as the potent active constituents of EGb761 in terms of their inhibition of Aβ42 aggregation and destabilization of the fibrils. Although quantitative mass spectroscopic analysis revealed that the catechins and procyanidins are only present in low concentrations in EGb761, these components should be studied in greater detail because of their potent inhibitory effects towards Aβ42 aggregation and their ability to destabilize preformed fibrils, especially during the quality control of Ginkgo leaves and the manufacture of Ginkgo products. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessCommunication

C5-Azobenzene-substituted 2'-Deoxyuridine-containing Oligodeoxynucleotides for Photo-Switching Hybridization

by Shohei Mori, Kunihiko Morihiro and Satoshi Obika

Molecules 2014, 19(4), 5109-5118; https://doi.org/10.3390/molecules19045109 - 22 Apr 2014

Cited by 18 | Viewed by 7048

Abstract

A new photoisomeric nucleoside dU^Az bearing an azobenzene group at the C5-position of 2'-deoxyuridine was designed and synthesized. Photoisomerization of dU^Azin oligodeoxynucleotides can be achieved rapidly and selectively with 365 nm (forward) and 450 nm (backward) irradiation. Thermal denaturation experiments [...] Read more.

A new photoisomeric nucleoside dU^Az bearing an azobenzene group at the C5-position of 2'-deoxyuridine was designed and synthesized. Photoisomerization of dU^Azin oligodeoxynucleotides can be achieved rapidly and selectively with 365 nm (forward) and 450 nm (backward) irradiation. Thermal denaturation experiments revealed that dU^Az stabilized the duplex in the cis-form and destabilized it in the trans-form with mismatch discrimination ability comparable to thymidine. These results indicate that dU^Az could be a powerful material for reversibly manipulating nucleic acid hybridization with spatiotemporal control. Full article

(This article belongs to the Special Issue Molecular Switches)

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Open AccessReview

Natural Dibenzo-α-Pyrones and Their Bioactivities

by Ziling Mao, Weibo Sun, Linyun Fu, Haiyu Luo, Daowan Lai and Ligang Zhou

Molecules 2014, 19(4), 5088-5108; https://doi.org/10.3390/molecules19045088 - 22 Apr 2014

Cited by 85 | Viewed by 13183

Abstract

Natural dibenzo-α-pyrones are an important group of metabolites derived from fungi, mycobionts, plants and animal feces. They exhibit a variety of biological activities such as toxicity on human and animals, phytotoxicity as well as cytotoxic, antioxidant, antiallergic, antimicrobial, antinematodal, and acetylcholinesterase inhibitory properties. [...] Read more.

Natural dibenzo-α-pyrones are an important group of metabolites derived from fungi, mycobionts, plants and animal feces. They exhibit a variety of biological activities such as toxicity on human and animals, phytotoxicity as well as cytotoxic, antioxidant, antiallergic, antimicrobial, antinematodal, and acetylcholinesterase inhibitory properties. Dibenzo-α-pyrones are biosynthesized via the polyketide pathway in microorganisms or metabolized from plant-derived ellagitannins and ellagic acid by intestinal bacteria. At least 53 dibenzo-α-pyrones have been reported in the past few decades. This mini-review aims to briefly summarize the occurrence, biosynthesis, biotransformation, as well as their biological activities and functions. Some considerations related to synthesis, production and applications of dibenzo-α-pyrones are also discussed. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Ruthenium^II Complexes bearing Fused Polycyclic Ligands: From Fundamental Aspects to Potential Applications

by Ludovic Troian-Gautier and Cécile Moucheron

Molecules 2014, 19(4), 5028-5087; https://doi.org/10.3390/molecules19045028 - 22 Apr 2014

Cited by 64 | Viewed by 17206

Abstract

In this review, we first discuss the photophysics reported in the literature for mononuclear ruthenium complexes bearing ligands with extended aromaticity such as dipyrido[3,2-a:2',3'-c]phenazine (DPPZ), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]-phenazine (TPPHZ), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]acridine (TPAC), 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene (PHEHAT) 9,11,20,22-tetraaza- tetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (TATPP), etc. Photophysical properties of binuclear and polynuclear complexes based [...] Read more.

In this review, we first discuss the photophysics reported in the literature for mononuclear ruthenium complexes bearing ligands with extended aromaticity such as dipyrido[3,2-a:2',3'-c]phenazine (DPPZ), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]-phenazine (TPPHZ), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]acridine (TPAC), 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene (PHEHAT) 9,11,20,22-tetraaza- tetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (TATPP), etc. Photophysical properties of binuclear and polynuclear complexes based on these extended ligands are then reported. We finally develop the use of binuclear complexes with extended π-systems for applications such as photocatalysis. Full article

(This article belongs to the Special Issue Ruthenium Complex)

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Open AccessArticle

Biocompatible Fe₃O₄ Increases the Efficacy of Amoxicillin Delivery against Gram-Positive and Gram-Negative Bacteria

by Alexandru Mihai Grumezescu, Monica Cartelle Gestal, Alina Maria Holban, Valentina Grumezescu, Bogdan Ștefan Vasile, Laurențiu Mogoantă, Florin Iordache, Coralia Bleotu and George Dan Mogoșanu

Molecules 2014, 19(4), 5013-5027; https://doi.org/10.3390/molecules19045013 - 22 Apr 2014

Cited by 65 | Viewed by 10019

Abstract

This paper reports the synthesis and characterization of amoxicillin- functionalized magnetite nanostructures (Fe₃O₄@AMO), revealing and discussing several biomedical applications of these nanomaterials. Our results proved that 10 nm Fe₃O₄@AMO nanoparticles does not alter the normal [...] Read more.

This paper reports the synthesis and characterization of amoxicillin- functionalized magnetite nanostructures (Fe₃O₄@AMO), revealing and discussing several biomedical applications of these nanomaterials. Our results proved that 10 nm Fe₃O₄@AMO nanoparticles does not alter the normal cell cycle progression of cultured diploid cells, and an in vivo murine model confirms that the nanostructures disperse through the host body and tend to localize in particular sites and organs. The nanoparticles were found clustered especially in the lungs, kidneys and spleen, next to the blood vessels at this level, while being totally absent in the brain and liver, suggesting that they are circulated through the blood flow and have low toxicity. Fe₃O₄@AMO has the ability to be easily circulated through the body and optimizations may be done so these nanostructures cluster to a specific target region. Functionalized magnetite nanostructures proved a great antimicrobial effect, being active against both the Gram positive pathogen S. aureus and the Gram negative pathogen E. coli. The fabricated nanostructures significantly reduced the minimum inhibitory concentration (MIC) of the active drug. This result has a great practical relevance, since the functionalized nanostructures may be used for decreasing the therapeutic doses which usually manifest great severe side effects, when administrated in high doses. Fe₃O₄@AMO represents also a suitable approach for the development of new alternative strategies for improving the activity of therapeutic agents by targeted delivery and controlled release. Full article

(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)

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Open AccessArticle

Surface-Functionalized Hyperbranched Poly(Amido Acid) Magnetic Nanocarriers for Covalent Immobilization of a Bacterial γ-Glutamyltranspeptidase

by Tzong-Yuan Juang, Shao-Ju Kan, Yi-Yu Chen, Yi-Lin Tsai, Min-Guan Lin and Long-Liu Lin

Molecules 2014, 19(4), 4997-5012; https://doi.org/10.3390/molecules19044997 - 22 Apr 2014

Cited by 26 | Viewed by 7176

Abstract

In this study, we synthesized water-soluble hyperbranched poly(amido acid)s (HBPAAs) featuring multiple terminal CO₂H units and internal tertiary amino and amido moieties and then used them in conjunction with an in situ Fe^2+/Fe³⁺ co-precipitation process to prepare organic/magnetic [...] Read more.

In this study, we synthesized water-soluble hyperbranched poly(amido acid)s (HBPAAs) featuring multiple terminal CO₂H units and internal tertiary amino and amido moieties and then used them in conjunction with an in situ Fe^2+/Fe³⁺ co-precipitation process to prepare organic/magnetic nanocarriers comprising uniformly small magnetic iron oxide nanoparticles (NP) incorporated within the globular HBPAAs. Transmission electron microscopy revealed that the HBPAA-γ-Fe₂O₃ NPs had dimensions of 6–11 nm, significantly smaller than those of the pristine γ-Fe₂O₃ (20–30 nm). Subsequently, we covalently immobilized a bacterial γ-glutamyltranspeptidase (BlGGT) upon the HBPAA-γ-Fe₂O₃ nanocarriers through the formation of amide linkages in the presence of a coupling agent. Magnetization curves of the HBPAA-γ-Fe₂O₃/BlGGT composites measured at 300 K suggested superparamagnetic characteristics, with a saturation magnetization of 52 emu g⁻¹. The loading capacity of BlGGT on the HBPAA-γ-Fe₂O₃ nanocarriers was 16 mg g⁻¹ support; this sample provided a 48% recovery of the initial activity. The immobilized enzyme could be recycled 10 times with 32% retention of the initial activity; it had stability comparable with that of the free enzyme during a storage period of 63 days. The covalent immobilization and stability of the enzyme and the magnetization provided by the HBPAA-γ-Fe₂O₃ NPs suggests that this approach could be an economical means of depositing bioactive enzymes upon nanocarriers for BlGGT-mediated bio-catalysis. Full article

(This article belongs to the Special Issue Enzyme Immobilization)

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Open AccessArticle

High Efficiency Acetylcholinesterase Immobilization on DNA Aptamer Modified Surfaces

by Orada Chumphukam, Thao T. Le and Anthony E. G. Cass

Molecules 2014, 19(4), 4986-4996; https://doi.org/10.3390/molecules19044986 - 21 Apr 2014

Cited by 13 | Viewed by 7484

Abstract

We report here the in vitro selection of DNA aptamers for electric eel acetylcholinesterase (AChE). One selected aptamer sequence (R15/19) has a high affinity towards the enzyme (K_d = 157 ± 42 pM). Characterization of the aptamer showed its binding is not [...] Read more.

We report here the in vitro selection of DNA aptamers for electric eel acetylcholinesterase (AChE). One selected aptamer sequence (R15/19) has a high affinity towards the enzyme (K_d = 157 ± 42 pM). Characterization of the aptamer showed its binding is not affected by low ionic strength (~20 mM), however significant reduction in affinity occurred at high ionic strength (~1.2 M). In addition, this aptamer does not inhibit the catalytic activity of AChE that we exploit through immobilization of the DNA on a streptavidin-coated surface. Subsequent immobilization of AChE by the aptamer results in a 4-fold higher catalytic activity when compared to adsorption directly on to plastic. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

Microsomal Prostaglandin E Synthase-1 Deficiency Exacerbates Pulmonary Fibrosis Induced by Bleomycin in Mice

by Bo Wei, Linhong Cai, Dan Sun, Yanhua Wang, Cairui Wang, Xiaoyu Chai, Feng Xie, Ming Su, Fangrui Ding, Jie Liu, Jichun Yang, Youfei Guan and Xinmin Liu

Molecules 2014, 19(4), 4967-4985; https://doi.org/10.3390/molecules19044967 - 21 Apr 2014

Cited by 12 | Viewed by 7893

Abstract

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH₂) to prostaglandin E2 (PGE₂), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. [...] Read more.

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH₂) to prostaglandin E2 (PGE₂), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1⁻^/−) mice exhibited more severe fibrotic lesions with a decrease in PGE₂ content in lungs after bleomycin treatment when compared with wild type (mPGES-1^+/+) mice. The mPGES-1 expression levels and PGE₂ content were also decreased in bleomycin-treated mPGES-1^+/+ mice compared to saline-treated mPGES-1^+/+ mice. Moreover, in both mPGES-1⁻^/− and mPGES-1^+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-β1 (TGF-β1)-induced α-smooth muscle actin (α-SMA) protein expression, and the increase was reversed by treatment of PGE₂, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE₂-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients. Full article

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Open AccessArticle

Characterization of Natural Aryl Hydrocarbon Receptor Agonists from Cassia Seed and Rosemary

by Yoshiaki Amakura, Morio Yoshimura, Masashi Takaoka, Haruka Toda, Tomoaki Tsutsumi, Rieko Matsuda, Reiko Teshima, Masafumi Nakamura, Hiroshi Handa and Takashi Yoshida

Molecules 2014, 19(4), 4956-4966; https://doi.org/10.3390/molecules19044956 - 17 Apr 2014

Cited by 14 | Viewed by 7121

Abstract

Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR) reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the [...] Read more.

Many recent studies have suggested that activation of the aryl hydrocarbon receptor (AhR) reduces immune responses, thus suppressing allergies and autoimmune diseases. In our continuing study on natural AhR agonists in foods, we examined the influence of 37 health food materials on the AhR using a reporter gene assay, and found that aqueous ethanol extracts of cassia seed and rosemary had particularly high AhR activity. To characterize the AhR-activating substances in these samples, the chemical constituents of the respective extracts were identified. From an active ethyl acetate fraction of the cassia seed extract, eight aromatic compounds were isolated. Among these compounds, aurantio-obtusin, an anthraquinone, elicited marked AhR activation. Chromatographic separation of an active ethyl acetate fraction of the rosemary extract gave nine compounds. Among these compounds, cirsimaritin induced AhR activity at 10–10² μM, and nepitrin and homoplantagenin, which are flavone glucosides, showed marked AhR activation at 10–10³ μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Anti-Proliferative and Apoptosis-Inducing Effects of Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic Ester in Human Breast Tumor MCF-7 Cells

by Chu Chu, Jialin Xu, Dongping Cheng, Xingnuo Li, Shengqiang Tong, Jizong Yan and Qingyong Li

Molecules 2014, 19(4), 4941-4955; https://doi.org/10.3390/molecules19044941 - 17 Apr 2014

Cited by 24 | Viewed by 7751

Abstract

Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester (CPT6) is a novel semi-synthetic analog of camptothecin. In a previous report, CPT6 possessed higher cytotoxic activity in vitro towards human breast tumor MCF-7 cells than topotecan. In this study, the antitumor activity of CPT6 on the human breast [...] Read more.

Camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester (CPT6) is a novel semi-synthetic analog of camptothecin. In a previous report, CPT6 possessed higher cytotoxic activity in vitro towards human breast tumor MCF-7 cells than topotecan. In this study, the antitumor activity of CPT6 on the human breast tumor MCF-7 cell line was analyzed using the MTT method. The underlying mechanism of CPT6 action was investigated by analyzing the cell cycle distribution, apoptotic proportion, changes in mitochondrial membrane potential, and intracellular Ca²⁺ concentration using flow cytometry. Nuclear and mitochondrial morphologies were also observed by laser scanning confocal and transmission electron microscopy. DNA damage was observed in MCF-7 cells treated with CPT6. Low-dose CPT6 had a significant cytotoxic effect and could inhibit proliferation and induce apoptosis in MCF-7 cells, possibly through cell nucleus fragmentation and DNA damage. CPT6 thus appears to display potent antitumor activity against human breast tumor MCF-7 cells via the induction of apoptosis, and may be a useful alternative drug for breast cancer therapy. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 19, Issue 4 (April 2014) – 100 articles , Pages 3851-5458

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