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Molecules, Volume 21, Issue 3 (March 2016)

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Cover Story cis- and trans-Isomers of [PtCl2(NCR)2] (R = NMe2, N(C5H10), Ph, CH2Ph) were examined as catalysts [...] Read more.
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Editorial

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Open AccessEditorial Coumarins, Xanthones and Related Compounds
Molecules 2016, 21(3), 341; https://doi.org/10.3390/molecules21030341
Received: 7 March 2016 / Accepted: 8 March 2016 / Published: 10 March 2016
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Abstract
It has long been known that coumarins (γ-pyrones) and xanthones (α-pyrones) together form a large class of naturally occurring compounds exhibiting a wide range of biological activities.[...] Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Novel Gold Nanoparticles Reduced by Sargassum glaucescens: Preparation, Characterization and Anticancer Activity
Molecules 2016, 21(3), 123; https://doi.org/10.3390/molecules21030123
Received: 24 September 2015 / Revised: 6 January 2016 / Accepted: 12 January 2016 / Published: 1 March 2016
Cited by 4 | PDF Full-text (4052 KB) | HTML Full-text | XML Full-text
Abstract
The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized
[...] Read more.
The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized AuNPs were stable and small at 3.65 ± 1.69 nm in size. The in vitro anticancer effect of SG-stabilized AuNPs was determined on cervical (HeLa), liver (HepG2), breast (MDA-MB-231) and leukemia (CEM-ss) cell lines using fluorescence microscopy, flow cytometry, caspase activity determination, and MTT assays. After 72 h treatment, SG-stabilized AuNPs was shown to be significant (p < 0.05) cytotoxic to the cancer cells in a dose- and time-dependent manner. The IC50 values of SG-stabilized AuNPs on the HeLa, HepG2, CEM-ss, MDA-MB-231 cell lines were 4.75 ± 1.23, 7.14 ± 1.45, 10.32 ± 1.5, and 11.82 ± 0.9 μg/mL, respectively. On the other hand, SG-stabilized AuNPs showed no cytotoxic effect towards the normal human mammary epithelial cells (MCF-10A). SG-stabilized AuNPs significantly (p < 0.05) arrest HeLa cell cycle at G2/M phase and significantly (p < 0.05) activated caspases-3 and -9 activities. The anticancer effect of SG-stabilized AuNPs is via the intrinsic apoptotic pathway. The study showed that SG-stabilized AuNPs is a good candidate to be developed into a chemotherapeutic compound for the treatment of cancers especially cervical cancer. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
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Open AccessArticle Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents
Molecules 2016, 21(3), 164; https://doi.org/10.3390/molecules21030164
Received: 6 January 2016 / Accepted: 25 January 2016 / Published: 29 February 2016
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Abstract
New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy)
[...] Read more.
New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Transcriptome Sequencing and Development of Genic SSR Markers of an Endangered Chinese Endemic Genus Dipteronia Oliver (Aceraceae)
Molecules 2016, 21(3), 166; https://doi.org/10.3390/molecules21030166
Received: 11 December 2015 / Revised: 25 January 2016 / Accepted: 26 January 2016 / Published: 23 February 2016
Cited by 6 | PDF Full-text (1083 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dipteronia Oliver (Aceraceae) is an endangered Chinese endemic genus consisting of two living species, Dipteronia sinensis and Dipteronia dyeriana. However, studies on the population genetics and evolutionary analyses of Dipteronia have been hindered by limited genomic resources and genetic markers.
[...] Read more.
Dipteronia Oliver (Aceraceae) is an endangered Chinese endemic genus consisting of two living species, Dipteronia sinensis and Dipteronia dyeriana. However, studies on the population genetics and evolutionary analyses of Dipteronia have been hindered by limited genomic resources and genetic markers. Here, the generation, de novo assembly and annotation of transcriptome datasets, and a large set of microsatellite or simple sequence repeat (SSR) markers derived from Dipteronia have been described. After Illumina pair-end sequencing, approximately 93.2 million reads were generated and assembled to yield a total of 99,358 unigenes. A majority of these unigenes (53%, 52,789) had at least one blast hit against the public protein databases. Further, 12,377 SSR loci were detected and 4179 primer pairs were designed for experimental validation. Of these 4179 primer pairs, 435 primer pairs were randomly selected to test polymorphism. Our results show that products from 132 primer pairs were polymorphic, in which 97 polymorphic SSR markers were further selected to analyze the genetic diversity of 10 natural populations of Dipteronia. The identification of SSR markers during our research will provide the much valuable data for population genetic analyses and evolutionary studies in Dipteronia. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessCommunication In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae
Molecules 2016, 21(3), 190; https://doi.org/10.3390/molecules21030190
Received: 4 January 2016 / Accepted: 2 February 2016 / Published: 23 February 2016
Cited by 4 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models
[...] Read more.
Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence), as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC10. Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time- and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Cytotoxic 1,3-Thiazole and 1,2,4-Thiadiazole Alkaloids from Penicillium oxalicum: Structural Elucidation and Total Synthesis
Molecules 2016, 21(3), 232; https://doi.org/10.3390/molecules21030232
Received: 25 January 2016 / Revised: 14 February 2016 / Accepted: 15 February 2016 / Published: 26 February 2016
Cited by 5 | PDF Full-text (2339 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic
[...] Read more.
Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle New Bufadienolides Isolated from the Roots of Kalanchoe daigremontiana (Crassulaceae)
Molecules 2016, 21(3), 243; https://doi.org/10.3390/molecules21030243
Received: 10 January 2016 / Revised: 11 February 2016 / Accepted: 19 February 2016 / Published: 24 February 2016
Cited by 4 | PDF Full-text (536 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An aqueous extract from the roots of Kalanchoe daigremontiana turned out to be a rich source of bufadienolides. The existing literature data relate mainly to the aerial parts of Kalanchoe but there is no information about the metabolic profile of the roots, which
[...] Read more.
An aqueous extract from the roots of Kalanchoe daigremontiana turned out to be a rich source of bufadienolides. The existing literature data relate mainly to the aerial parts of Kalanchoe but there is no information about the metabolic profile of the roots, which are also used in traditional medicine. Our investigation concerning the roots of K. daigremontiana led to the isolation and characterization of eight new bufadienolides, namely 1β,3β,5β,14β,19-pentahydroxybufa-20,22-dienolide (1), 19-(acetyloxy)-1β,3β,5β,14β-tetrahydroxybufa-20,22-dienolide (2), 3β-O-α-l-rhamno-pyranosyl-5β,11α,14β,19-tetrahydroxybufa-20,22-dienolide (3), 19-(acetyloxy)-3β,5β,11α,14β-tetrahydroxybufa-20,22-dienolide (4), 3β,5β,11α,14β,19-pentahydroxy-12-oxo-bufa-20,22-dienolide (5), 19-(acetyloxy)-3β,5β,11α,14β-tetrahydroxy-12-oxo-bufa-20,22-dienolide (6), 19-(acetyloxy)-1β,3β,5β,11α,14β-pentahydroxy-12-oxo-bufa-20,22-dienolide (7) and 1β-(acetyloxy)-3β,5β,11α,14β,19-pentahydroxy-12-oxo-bufa-20,22-dienolide (8), together with seven known compounds: 11α,19-dihydroxytelocinobufagin (9), bersaldegenin-1-acetate (10), daigredorigenin-3-acetate (11), bersaldegenin-1,3,5-orthoacetate (12), bryotoxin B (13), bryophyllin B (14) and bersaldegenin (15). The structures were established applying extensive 1D- and 2D-NMR and MS spectroscopic analyses. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Phenolic Compounds in Chilean Mistletoe (Quintral, Tristerix tetrandus) Analyzed by UHPLC–Q/Orbitrap/MS/MS and Its Antioxidant Properties
Molecules 2016, 21(3), 245; https://doi.org/10.3390/molecules21030245
Received: 25 January 2016 / Revised: 11 February 2016 / Accepted: 18 February 2016 / Published: 23 February 2016
Cited by 13 | PDF Full-text (3036 KB) | HTML Full-text | XML Full-text
Abstract
Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses.
[...] Read more.
Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses. In this work the metabolites of a Chilean mistletoe endemic to the VIII region of Chile were investigated for the first time using UHPLC mass analysis (UHPLC-PDA-HESI-Orbitrap MSn). The anthocyanins, together with the non-pigmented phenolics were fingerprinted and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA), and total content of phenolics, flavonoids and anthocyanins measured by spectroscopic methods. Six anthocyanins were identified, and among them, the 3-O-glycosides of delphinidin and cyanidin were the major ones. In addition, several phenolic acids (including feruloylquinic acid, feruloyl glucose, chlorogenic acid) and several flavonols (luteolin, quercetin, apigenin, isorhamnetin and glycoside derivatives) were also identified. The mistletoe leaves showed the highest antioxidant activity as measured by the DPPH radical bleaching, ferric reducing antioxidant power and superoxide anion scavenging activity tests (13.38 ± 0.47 µg/mL, 125.32 ± 5.96 µmolTE/g DW and 84.06 ± 4.59 at 100 µg/mL, respectively). Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Exotic Vegetable Oils for Cosmetic O/W Nanoemulsions: In Vivo Evaluation
Molecules 2016, 21(3), 248; https://doi.org/10.3390/molecules21030248
Received: 11 November 2015 / Revised: 13 January 2016 / Accepted: 5 February 2016 / Published: 24 February 2016
Cited by 4 | PDF Full-text (2481 KB) | HTML Full-text | XML Full-text
Abstract
Oil-in-water nanoemulsions are stable systems with droplet sizes in the 20–200 nm range. The physicochemical properties of these systems may be influenced by the addition of additives. Thus, the influence of ethoxylated (EL) and acetylated lanolin (AL) addition on the droplet size, pH
[...] Read more.
Oil-in-water nanoemulsions are stable systems with droplet sizes in the 20–200 nm range. The physicochemical properties of these systems may be influenced by the addition of additives. Thus, the influence of ethoxylated (EL) and acetylated lanolin (AL) addition on the droplet size, pH values, electrical conductivity and stability of nanoemulsions was investigated. Then, effect of nano-emulsions additives with EL (NE-EL) or AL (NE-AL) in hydration, oiliness and pH of the skin were evaluated. Nanoemulsion safety was evaluated through the observation of no undesirable effects after skin formulation application. Both additives caused changes in droplet size and electrical conductivity, but not in pH values. Nanoemulsions containing up to 6.0% ethoxylated lanolin and 2.0% acetylated lanolin remained stable after centrifugation tests. Higher concentrations of the additives made the nanoemulsions unstable. Stability tests showed that ethoxylated lanolin produced more stable nanoemulsions then acetylated lanolin and that the major instability phenomenon occurring in these systems is coalescence at elevated temperatures. Nanoemulsion-based lanolin derivatives increased skin hydration and oiliness and did not change cutaneous pH values. These formulations are non-toxic since they did not cause any irritation on the skin surface after nanoemulsion application, showing potential as carriers for pharmaceuticals and cosmetic applications. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
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Open AccessArticle Synthesis of 5,10-bis(Trifluoromethyl) Substituted β-Octamethylporphyrins and Central-Metal-Dependent Solvolysis of Their meso-Trifluoromethyl Groups
Molecules 2016, 21(3), 252; https://doi.org/10.3390/molecules21030252
Received: 9 January 2016 / Revised: 15 February 2016 / Accepted: 19 February 2016 / Published: 23 February 2016
Cited by 1 | PDF Full-text (951 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
5,10-Bistrifluoromethyl substituted β-octamethylporphyrins were synthesized via a scrambling side reaction of a dipyrromethane precursor in the presence of a large excess of trifluoroacetic acid. Compared with the trans-analogs, the cis-analogs of meso-trifluoromethyl β-octaalkylporphyrin showed more red-shifted absorption bands. These meso
[...] Read more.
5,10-Bistrifluoromethyl substituted β-octamethylporphyrins were synthesized via a scrambling side reaction of a dipyrromethane precursor in the presence of a large excess of trifluoroacetic acid. Compared with the trans-analogs, the cis-analogs of meso-trifluoromethyl β-octaalkylporphyrin showed more red-shifted absorption bands. These meso-trifluoromethyl derivatives of β-octaalkylporphyrins underwent smooth metalation, similar to other common porphyrins, however, the corresponding zinc complexes underwent a type of solvolysis, whereby the trifluoromethyl groups were converted into methoxycarbonyl groups by the methanol used as solvent. UV-visible absorption spectra and X-ray crystal structure analyses revealed that the presence of a methoxycarbonyl substituent did not influence the deformation of the molecular framework and its absorption properties; this is because the methoxycarbonyl has a planar and perpendicular geometry, as opposed to the relatively bulky trifluoromethyl substituent. Full article
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Open AccessArticle Preparation and Biological Evaluation of Two Novel Platinum(II) Complexes Based on the Ligands of Dipicolyamine Bisphosphonate Esters
Molecules 2016, 21(3), 255; https://doi.org/10.3390/molecules21030255
Received: 30 December 2015 / Revised: 1 February 2016 / Accepted: 2 February 2016 / Published: 24 February 2016
Cited by 4 | PDF Full-text (4121 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were
[...] Read more.
Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were evaluated and compared with cisplatin (CDDP). Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP. Full article
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Open AccessArticle Chitosan Nanoparticles as Carriers for the Delivery of ΦKAZ14 Bacteriophage for Oral Biological Control of Colibacillosis in Chickens
Molecules 2016, 21(3), 256; https://doi.org/10.3390/molecules21030256
Received: 30 November 2015 / Revised: 26 January 2016 / Accepted: 10 February 2016 / Published: 14 March 2016
Cited by 4 | PDF Full-text (1039 KB) | HTML Full-text | XML Full-text
Abstract
The use of chitosan as a delivery carrier has attracted much attention in recent years. In this study, chitosan nanoparticles (CS-NP) and chitosan-ΦKAZ14 bacteriophage-loaded nanoparticles (C-ΦKAZ14 NP) were prepared by a simple coercavation method and characterized. The objective was to achieve an effective
[...] Read more.
The use of chitosan as a delivery carrier has attracted much attention in recent years. In this study, chitosan nanoparticles (CS-NP) and chitosan-ΦKAZ14 bacteriophage-loaded nanoparticles (C-ΦKAZ14 NP) were prepared by a simple coercavation method and characterized. The objective was to achieve an effective protection of bacteriophage from gastric acids and enzymes in the chicken gastrointestinal tract. The average particle sizes for CS-NP and C-ΦKAZ14 NP were 188 ± 7.4 and 176 ± 3.2 nm, respectively. The zeta potentials for CS-NP and C-ΦKAZ14 NP were 50 and 60 mV, respectively. Differential scanning calorimetry (DSC) of C-ΦKAZ14 NP gave an onset temperature of −17.17 °C with a peak at 17.32 °C and final end set of 17.41 °C, while blank chitosan NP had an onset of −20.00 °C with a peak at −19.78 °C and final end set at −20.47. FT-IR spectroscopy data of both CS-NP and C-ΦKAZ14 NP were the same. Chitosan nanoparticles showed considerable protection of ΦKAZ14 bacteriophage against degradation by enzymes as evidenced in gel electrophoresis, whereby ΦKAZ14 bacteriophage encapsulated in chitosan nanoparticles were protected whereas the naked ΦKAZ14 bacteriophage were degraded. C-ΦKAZ14 NP was non-toxic as shown by a chorioallantoic membrane (CAM) toxicity assay. It was concluded that chitosan nanoparticles could be a potent carrier of ΦKAZ14 bacteriophage for oral therapy against colibacillosis in poultry. Full article
(This article belongs to the Special Issue Chitin, Chitosan and Related Enzymes)
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Open AccessArticle Typical Monoterpenes as Insecticides and Repellents against Stored Grain Pests
Molecules 2016, 21(3), 258; https://doi.org/10.3390/molecules21030258
Received: 19 October 2015 / Accepted: 4 November 2015 / Published: 23 February 2016
Cited by 5 | PDF Full-text (1158 KB) | HTML Full-text | XML Full-text
Abstract
Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species.
[...] Read more.
Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species. They were more efficient in their fumigant activity against C. maculatus than against S. zeamais, while this profile of action was inverted when considering the repellent activities. Eugenol was one the most effective fumigants against both insects and one the most effective repellent against C. maculatus, while citronellal and geranial were one the most effective repellents against S. zeamais. Functional and positional isomerism of the monoterpenes pairs appears to exert little or no influence on theirs effects, especially in case of repellency. The validation of the insecticidal/repellent efficacy of isolated monoterpenes may permit a more advantageous, rapid, economic and optimized approach to the identification of promising oils for commercial formulations when combined with ethnobotanical strategies. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Statistical Correlations between HPLC Activity-Based Profiling Results and NMR/MS Microfraction Data to Deconvolute Bioactive Compounds in Mixtures
Molecules 2016, 21(3), 259; https://doi.org/10.3390/molecules21030259
Received: 25 November 2015 / Revised: 18 January 2016 / Accepted: 25 January 2016 / Published: 24 February 2016
Cited by 3 | PDF Full-text (1540 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and
[...] Read more.
Recent approaches in natural product (NP) research are leading toward the discovery of bioactive chemical entities at the microgram level. In comparison to classical large scale bioassay-guided fractionation, the use of LC-MS metabolite profiling in combination with microfractionation for both bioactivity profiling and NMR analysis, allows the identification of bioactive compounds at a very early stage. In that context, this study aims to assess the potential of statistic correlation analysis to enable unambiguous identification of features related to bioactive compounds in mixtures, without the need for complete isolation. For that purpose, a mixture of NPs was microfractionated by rapid small-scale semi-preparative HPLC for proof-of-concept. UHPLC-ESI-TOFMS profiles, micro-flow CapNMR spectra and a cancer chemopreventive assay carried out on every microfraction were analysed by statistical correlations. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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Open AccessArticle Antidepressant Potential of Chlorogenic Acid-Enriched Extract from Eucommia ulmoides Oliver Bark with Neuron Protection and Promotion of Serotonin Release through Enhancing Synapsin I Expression
Molecules 2016, 21(3), 260; https://doi.org/10.3390/molecules21030260
Received: 28 December 2015 / Revised: 17 February 2016 / Accepted: 18 February 2016 / Published: 25 February 2016
Cited by 7 | PDF Full-text (3863 KB) | HTML Full-text | XML Full-text
Abstract
Eucommia ulmoides Oliver (E. ulmoides) is a traditional Chinese medicine with many beneficial effects, used as a tonic medicine in China and other countries. Chlorogenic acid (CGA) is an important compound in E. ulmoides with neuroprotective, cognition improvement and other pharmacological
[...] Read more.
Eucommia ulmoides Oliver (E. ulmoides) is a traditional Chinese medicine with many beneficial effects, used as a tonic medicine in China and other countries. Chlorogenic acid (CGA) is an important compound in E. ulmoides with neuroprotective, cognition improvement and other pharmacological effects. However, it is unknown whether chlorogenic acid-enriched Eucommia ulmoides Oliver bark has antidepressant potential through neuron protection, serotonin release promotion and penetration of blood-cerebrospinal fluid barrier. In the present study, we demonstrated that CGA could stimulate axon and dendrite growth and promote serotonin release through enhancing synapsin I expression in the cells of fetal rat raphe neurons in vitro. More importantly, CGA-enriched extract of E. ulmoides (EUWE) at 200 and 400 mg/kg/day orally administered for 7 days showed antidepressant-like effects in the tail suspension test of KM mice. Furthermore, we also found CGA could be detected in the the cerebrospinal fluid of the rats orally treated with EUWE and reach the level of pharmacological effect for neuroprotection by UHPLC-ESI-MS/MS. The findings indicate CGA is able to cross the blood-cerebrospinal fluid barrier to exhibit its neuron protection and promotion of serotonin release through enhancing synapsin I expression. This is the first report of the effect of CGA on promoting 5-HT release through enhancing synapsin I expression and CGA-enriched EUWE has antidepressant-like effect in vivo. EUWE may be developed as the natural drugs for the treatment of depression. Full article
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Open AccessArticle Au-Based Catalysts: Electrochemical Characterization for Structural Insights
Molecules 2016, 21(3), 261; https://doi.org/10.3390/molecules21030261
Received: 29 January 2016 / Revised: 19 February 2016 / Accepted: 22 February 2016 / Published: 25 February 2016
Cited by 3 | PDF Full-text (1789 KB) | HTML Full-text | XML Full-text
Abstract
Au-based catalysts are widely used in important processes because of their peculiar characteristics. The catalyst performance depends strongly on the nature and structure of the metal nanoparticles, especially in the case of bimetallic catalysts where synergistic effects between the two metals can be
[...] Read more.
Au-based catalysts are widely used in important processes because of their peculiar characteristics. The catalyst performance depends strongly on the nature and structure of the metal nanoparticles, especially in the case of bimetallic catalysts where synergistic effects between the two metals can be occasionally seen. In this paper, it is shown that electrochemical characterisation (cyclovoltammetry CV and electrochemical impedance spectroscopy EIS) of AuPd systems can be used to determine the presence of an electronic interaction between the two metals, thus providing a strong support in the determination of the nature of the synergy between Au and Pd in the liquid phase oxidation of alcohols. However, it seems likely that the strong difference in the catalytic behavior between the single metals and the bimetallic system is connected not only to the redox behaviour, but also to the energetic balance between the different elementary steps of the reaction. Full article
(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)
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Open AccessArticle Extraction, Preconcentration and Isolation of Flavonoids from Apocynum venetum L. Leaves Using Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with an Aqueous Biphasic System
Molecules 2016, 21(3), 262; https://doi.org/10.3390/molecules21030262
Received: 23 December 2015 / Revised: 17 February 2016 / Accepted: 19 February 2016 / Published: 4 March 2016
Cited by 11 | PDF Full-text (2102 KB) | HTML Full-text | XML Full-text
Abstract
Background: Ionic liquids (ILs) are considered as green solvents, and widely applied for the extraction of various compounds. Methods: The present research focuses on the extraction of flavonoids from Apocynum venetum L. leaves by ultrasound-assisted extraction (UAE). Several major influencing factors
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Background: Ionic liquids (ILs) are considered as green solvents, and widely applied for the extraction of various compounds. Methods: The present research focuses on the extraction of flavonoids from Apocynum venetum L. leaves by ultrasound-assisted extraction (UAE). Several major influencing factors were optimized. Then, an aqueous biphasic system (ABS) was applied for further isolation of flavonoids. Results: The flavonoids were mainly distributed in the top phase, while impurities were extracted to the bottom phase. The parameters influencing the extraction, namely type and concentration of salt, temperature, and pH, were studied in detail. Under optimized conditions (72.43% IL extract, 28.57% (NH4)2SO4, 25 °C temperature, pH 4.5), the preconcentration factor and extraction efficiency were found to be 3.78% and 93.35%, respectively. Conclusions: This simple and efficient methodology is expected to see great use in the extraction and isolation of pharmaceutically active components from medicinal plant resources. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle An Efficient Chemical Synthesis of Scutellarein: An in Vivo Metabolite of Scutellarin
Molecules 2016, 21(3), 263; https://doi.org/10.3390/molecules21030263
Received: 24 January 2016 / Revised: 17 February 2016 / Accepted: 22 February 2016 / Published: 25 February 2016
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Abstract
Scutellarein (2), which is an important in vivo metabolite of scutellarin (1), was synthesized from 3,4,5-trimethoxyphenol (3) in high yield in four steps. This strategy relies on acetylation, aldolization, cyclization and hydrolysis reactions, respectively. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting
Molecules 2016, 21(3), 265; https://doi.org/10.3390/molecules21030265
Received: 18 January 2016 / Revised: 15 February 2016 / Accepted: 22 February 2016 / Published: 29 February 2016
Cited by 6 | PDF Full-text (2724 KB) | HTML Full-text | XML Full-text
Abstract
Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products,
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Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach
Molecules 2016, 21(3), 266; https://doi.org/10.3390/molecules21030266
Received: 31 December 2015 / Revised: 29 January 2016 / Accepted: 1 February 2016 / Published: 25 February 2016
Cited by 4 | PDF Full-text (6380 KB) | HTML Full-text | XML Full-text
Abstract
A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these
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A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of Naphthalene-Based Push-Pull Molecules with a Heteroaromatic Electron Acceptor
Molecules 2016, 21(3), 267; https://doi.org/10.3390/molecules21030267
Received: 4 January 2016 / Revised: 18 February 2016 / Accepted: 22 February 2016 / Published: 2 March 2016
Cited by 4 | PDF Full-text (1573 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to
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Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to label protein aggregates of different compositions formed in the brain of patients suffering from neurodegenerative diseases like Alzheimer’s (AD). In continuation of our research we set our goal to find new FDDNP analogs, which would inherit optical and binding properties but hopefully show better specificity for tau protein aggregates, which are characteristic for neurodegeneration caused by repetitive mild trauma. In this work we report on the synthesis of new FDDNP analogs in which the acceptor group has been formally replaced with an aromatic five- or six-membered heterocycle. The heterocyclic moiety was annealed to the central naphthalene ring either by classical ring closure reactions or by modern transition metal-catalyzed coupling reactions. The chemical characterization, NMR spectra, and UV/vis properties of all new compounds are reported. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats
Molecules 2016, 21(3), 269; https://doi.org/10.3390/molecules21030269
Received: 19 December 2015 / Revised: 17 February 2016 / Accepted: 19 February 2016 / Published: 25 February 2016
Cited by 4 | PDF Full-text (2086 KB) | HTML Full-text | XML Full-text
Abstract
Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic
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Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Rapid Authentication of the Herbal Medicine Plant Species Aralia continentalis Kitag. and Angelica biserrata C.Q. Yuan and R.H. Shan Using ITS2 Sequences and Multiplex-SCAR Markers
Molecules 2016, 21(3), 270; https://doi.org/10.3390/molecules21030270
Received: 25 January 2016 / Revised: 24 February 2016 / Accepted: 24 February 2016 / Published: 29 February 2016
Cited by 8 | PDF Full-text (2884 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and Angelica biserrata (Angelicae Pubescentis Radix) are used in the same traditional medicine, namely Dok-Hwal in
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Accurate identification of the plant species that are present in herbal medicines is important for quality control. Although the dried roots of Aralia continentalis (Araliae Continentalis Radix) and Angelica biserrata (Angelicae Pubescentis Radix) are used in the same traditional medicine, namely Dok-Hwal in Korean and Du-Huo in Chinese, the medicines are described differently in the national pharmacopeia. Further confusion arises from the distribution of dried Levisticum officinale and Heracleum moellendorffii roots as the same medicine. Medicinal ingredients from all four plants are morphologically similar, and discrimination is difficult using conventional methods. Molecular identification methods offer rapidity and accuracy. The internal transcribed spacer 2 (ITS2) region of the nuclear ribosomal RNA gene (rDNA) was sequenced in all four plant species, and the sequences were used to design species-specific primers. Primers for each species were then combined to allow sample analysis in a single PCR reaction. Commercial herbal medicine samples were obtained from Korea and China and analyzed using the multiplex assay. The assay successfully identified authentic medicines and also identified inauthentic or adulterated samples. The multiplex assay will be a useful tool for identification of authentic Araliae Continentalis Radix and/or Angelicae Pubescentis Radix preparations in Korea and China. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Biological Validation of Novel Polysubstituted Pyrazole Candidates with in Vitro Anticancer Activities
Molecules 2016, 21(3), 271; https://doi.org/10.3390/molecules21030271
Received: 3 December 2015 / Revised: 16 February 2016 / Accepted: 19 February 2016 / Published: 26 February 2016
Cited by 14 | PDF Full-text (552 KB) | HTML Full-text | XML Full-text
Abstract
With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their
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With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their antiproliferative activity against 60 different human tumor cell lines was validated by the U.S. National Cancer Institute using a two stage process. The in vitro anticancer evaluation revealed that compound 9 showed increased potency toward most human tumor cell lines with GI50MG-MID = 3.59 µM, as compared to the standard drug sorafenib (GI50 MG-MID = 1.90 µM). At the same time, compounds 6a and 7 were selective against the HOP-92 cell line of non-small cell lung cancer with GI50 1.65 and 1.61 µM, respectively. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Structure Determination of Novel Oxidation Products from Epicatechin: Thearubigin-Like Molecules
Molecules 2016, 21(3), 273; https://doi.org/10.3390/molecules21030273
Received: 29 January 2016 / Revised: 20 February 2016 / Accepted: 23 February 2016 / Published: 26 February 2016
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Abstract
Following the oxidation of epicatechin (EC), three novel compounds and two known compounds were isolated. The chemical structures of these oxidation products were determined by mass spectrometry (MS) and various nuclear magnetic resonance (NMR) experiments, and the A-ring–B-ring linkage that is characteristic of
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Following the oxidation of epicatechin (EC), three novel compounds and two known compounds were isolated. The chemical structures of these oxidation products were determined by mass spectrometry (MS) and various nuclear magnetic resonance (NMR) experiments, and the A-ring–B-ring linkage that is characteristic of catechin was found in each molecule. Three compounds showed similar ultraviolet–visible (UV-Vis) spectra to EC, whereas two compounds showed different spectral absorption in the region between 300 and 500 nm. A similar spectrum was obtained for the thearubigin fraction prepared from a black tea infusion. This result suggests that the condensation reaction between the A-ring and B-ring is more important than reaction between B-rings for thearubigin formation. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Sesquiterpenoids from Chinese Agarwood Induced by Artificial Holing
Molecules 2016, 21(3), 274; https://doi.org/10.3390/molecules21030274
Received: 22 January 2016 / Revised: 22 February 2016 / Accepted: 23 February 2016 / Published: 26 February 2016
Cited by 5 | PDF Full-text (988 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR)
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Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The absolute configuration of compound 1 was determined by comparison of its measured CD curve with that of calculated data for 1 and ent-1. The NMR data of 3 were reported in this study for the first time. Compounds 1, 2, 4–6, together with the EtOAc extract showed moderate inhibitory activities against acetylcholinesterase, and compounds 4–6, 8 exhibited antibacterial activities against Staphylococcus aureus or Ralstonia solanacearum. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Quantitative Variation of Flavonoids and Diterpenes in Leaves and Stems of Cistus ladanifer L. at Different Ages
Molecules 2016, 21(3), 275; https://doi.org/10.3390/molecules21030275
Received: 21 January 2016 / Revised: 18 February 2016 / Accepted: 23 February 2016 / Published: 27 February 2016
Cited by 6 | PDF Full-text (994 KB) | HTML Full-text | XML Full-text
Abstract
The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of
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The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of the plant and they may be modified as a response to biotic and/or abiotic stress. As a consequence, the resistance state of a plant may vary in space and time. The secondary metabolites of Cistus ladanifer have been quantified in leaves and stems throughout autumn, winter, spring and summer, and at different ages of the plant. This study shows that there are significant differences between young leaves, mature leaves and stems, and between individuals of different ages. Young leaves show significantly greater synthesis of flavonoids and diterpenes than mature leaves and stems, with a clear seasonal variation, and the differences between leaves at different growth stages and stems is maintained during the quantified seasons. With respect to age, specimens under one year of age secreted significantly lower amounts of compounds. The variation in the composition of secondary metabolites between different parts of the plant, the season and the variations in age may determine the interactions of Cistus ladanifer with the biotic and abiotic factors to which it is exposed. Full article
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Open AccessArticle Synthesis and Bioactivities of Novel Pyrazole Oxime Derivatives Containing a 5-Trifluoromethylpyridyl Moiety
Molecules 2016, 21(3), 276; https://doi.org/10.3390/molecules21030276
Received: 1 February 2016 / Revised: 19 February 2016 / Accepted: 23 February 2016 / Published: 27 February 2016
Cited by 11 | PDF Full-text (596 KB) | HTML Full-text | XML Full-text
Abstract
In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus
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In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus cinnabarinus at a concentration of 200 μg/mL, and some designed compounds still showed excellent acaricidal activity against Tetranychus cinnabarinus at the concentration of 10 μg/mL, especially since the inhibition rates of compounds 8e, 8f, 8l, 8m, 8n, 8p, and 8q were all 100.00%. Interestingly, some target compounds exhibited moderate to good insecticidal activities against Plutella xylostella and Aphis craccivora at a concentration of 200 μg/mL; furthermore, compounds 8e and 8l possessed outstanding insecticidal activities against Plutella xylostella under the concentration of 50 μg/mL. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test
Molecules 2016, 21(3), 277; https://doi.org/10.3390/molecules21030277
Received: 26 January 2016 / Revised: 23 February 2016 / Accepted: 23 February 2016 / Published: 27 February 2016
Cited by 2 | PDF Full-text (1354 KB) | HTML Full-text | XML Full-text
Abstract
Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited
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Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Rhodium Porphyrin Bound to a Merrifield Resin as Heterogeneous Catalyst for the Cyclopropanation Reaction of Olefins
Molecules 2016, 21(3), 278; https://doi.org/10.3390/molecules21030278
Received: 4 February 2016 / Revised: 18 February 2016 / Accepted: 24 February 2016 / Published: 27 February 2016
Cited by 3 | PDF Full-text (412 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isomeric products. In this paper a meso-tetraphenylporphyrin
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Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isomeric products. In this paper a meso-tetraphenylporphyrin rhodium(III) chloride was bound to a Merrifield resin and used to catalyze the cyclopropanation reaction of nine olefins, giving good yields and selectivities of the final products and for the first time, a partial recycling of the catalyst. This new catalytic system will be tested in the future for the synthesis of natural products containing cyclopropyl ring. Full article
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Open AccessArticle 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice
Molecules 2016, 21(3), 279; https://doi.org/10.3390/molecules21030279
Received: 3 January 2016 / Revised: 21 February 2016 / Accepted: 23 February 2016 / Published: 27 February 2016
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Abstract
The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg−1·day−1), DNJ-40 (DNJ
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The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg−1·day−1), DNJ-40 (DNJ 40 mg·kg−1·day−1) and DNJ-80 (DNJ 80 mg·kg−1·day−1). All doses were treated intravenously by tail vein for four weeks. DNJ was observed to significantly reduce the levels of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and liver TG, as well as activities of serum alanine aminotransferase (ALT), and aspartate transaminase (AST); DNJ also alleviated macrovesicular steatosis and decreased tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) levels in liver tissue. Furthermore, DNJ treatment significantly increased hepatic glycogen content, the activities of hexokinase (HK), pyruvate kinase (PK) in liver tissue, and decreased the activities of glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, DNJ increased the phosphorylation of phosphatidylinositol 3 kinase (PI3K) on p85, protein kinase B (PKB) on Ser473, glycogen synthase kinase 3β (GSK-3β) on Ser9, and inhibited phosphorylation of glycogen synthase (GS) on Ser645 in liver tissue of db/db mice. These results demonstrate that DNJ can increase hepatic insulin sensitivity via strengthening of the insulin-stimulated PKB/GSK-3β signal pathway and by modulating glucose metabolic enzymes in db/db mice. Moreover, DNJ also can improve lipid homeostasis and attenuate hepatic steatosis in db/db mice. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Three New Sesquiterpenoids and One New Sesquiterpenoid Derivative from Chinese Eaglewood
Molecules 2016, 21(3), 281; https://doi.org/10.3390/molecules21030281
Received: 20 January 2016 / Revised: 22 February 2016 / Accepted: 23 February 2016 / Published: 27 February 2016
Cited by 2 | PDF Full-text (1037 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new sesquiterpenoids (13) and one new sesquiterpenoid derivative (4), along with three known sesquiterpenoids (57), were isolated from the 95% ethanolic extract of Chinese eaglewood [Aquilaria sinensis (Lour.) Gilg]. The structures
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Three new sesquiterpenoids (13) and one new sesquiterpenoid derivative (4), along with three known sesquiterpenoids (57), were isolated from the 95% ethanolic extract of Chinese eaglewood [Aquilaria sinensis (Lour.) Gilg]. The structures of these compounds were elucidated through extensive analysis of spectroscopic data including IR, NMR, HRESIMS, and X-ray diffraction experiments. In addition, the above new compounds were detected for their bioactivities against LPS-induced NO production in RAW 264.7 cells. Among them, compound 2 exhibited obvious anti-inflammatory activity with an IC50 value of 8.1 μM. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin
Molecules 2016, 21(3), 282; https://doi.org/10.3390/molecules21030282
Received: 31 December 2015 / Revised: 21 February 2016 / Accepted: 23 February 2016 / Published: 15 March 2016
Cited by 3 | PDF Full-text (6825 KB) | HTML Full-text | XML Full-text
Abstract
A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for
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A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32–40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
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Open AccessArticle Methanolic Extract of Pien Tze Huang Induces Apoptosis Signaling in Human Osteosarcoma MG63 Cells via Multiple Pathways
Molecules 2016, 21(3), 283; https://doi.org/10.3390/molecules21030283
Received: 16 January 2016 / Revised: 21 February 2016 / Accepted: 23 February 2016 / Published: 1 March 2016
Cited by 3 | PDF Full-text (2832 KB) | HTML Full-text | XML Full-text
Abstract
Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and
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Pien Tze Huang (PZH) is a well-known traditional Chinese formulation and has long been used as an alternative remedy for cancers in China and Southeast Asia. Recently, antitumor activity of PZH on several tumors have been increasingly reported, but its antitumor activity and the possible action mechanism on osteosarcoma remains unclear. After treatment with PZH, cell viability of MG-63 cells was dose-dependently inhibited compared to control cells. Moreover, a DNA ladder characteristic of apoptosis was observed in the cells treated with PZH, especially 500 μg/mL, 750 μg/mL. Further investigation showed that PZH treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and Bcl-xL expression. In addition, our results suggested that PZH activated PI3K/Akt signal pathway, and the phosphorylation of Akt and ERK1/2 were associated with the induction of apoptotic signaling. These results revealed that PZH possesses antitumoral activity on human osteosarcoma MG63 cells by manipulating apoptotic signaling and multiple pathways. It is suggested that PZH alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication On the Traceability of Commercial Saffron Samples Using 1H-NMR and FT-IR Metabolomics
Molecules 2016, 21(3), 286; https://doi.org/10.3390/molecules21030286
Received: 16 December 2015 / Revised: 24 February 2016 / Accepted: 25 February 2016 / Published: 29 February 2016
Cited by 12 | PDF Full-text (438 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In previous works on authentic samples of saffron of known history (harvest and processing year, storage conditions, and length of time) some biomarkers were proposed using both FT-IR and NMR metabolomics regarding the shelf life of the product. This work addresses the difficulties
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In previous works on authentic samples of saffron of known history (harvest and processing year, storage conditions, and length of time) some biomarkers were proposed using both FT-IR and NMR metabolomics regarding the shelf life of the product. This work addresses the difficulties to trace back the “age” of commercial saffron samples of unknown history, sets a limit value above which these products can be considered substandard, and offers a useful tool to combat saffron mislabeling and fraud with low-quality saffron material. Investigations of authentic and commercial saffron samples of different origin and harvest year, which had been stored under controlled conditions for different lengths of time, allowed a clear-cut clustering of samples in two groups according to the storage period irrespectively of the provenience. In this respect, the four-year cut off point proposed in our previous work assisted to trace back the “age” of unknown samples and to check for possible mislabeling practices. Full article
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Open AccessArticle Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins
Molecules 2016, 21(3), 287; https://doi.org/10.3390/molecules21030287
Received: 16 January 2016 / Revised: 23 February 2016 / Accepted: 25 February 2016 / Published: 29 February 2016
Cited by 4 | PDF Full-text (1535 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants
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The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). Nε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and Nε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme’s binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide. Full article
(This article belongs to the Special Issue Biomolecules Modification)
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Open AccessArticle Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations
Molecules 2016, 21(3), 288; https://doi.org/10.3390/molecules21030288
Received: 30 January 2016 / Revised: 19 February 2016 / Accepted: 24 February 2016 / Published: 29 February 2016
Cited by 12 | PDF Full-text (1824 KB) | HTML Full-text | XML Full-text
Abstract
The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement,
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The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm). The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (Foscan©) already used in the photodynamic therapy (PDT) protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents. Full article
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Open AccessArticle Photochemistry of the α-Al2O3-PETN Interface
Molecules 2016, 21(3), 289; https://doi.org/10.3390/molecules21030289
Received: 13 January 2016 / Revised: 21 February 2016 / Accepted: 23 February 2016 / Published: 29 February 2016
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Abstract
Optical absorption measurements are combined with electronic structure calculations to explore photochemistry of an α-Al2O3-PETN interface formed by a nitroester (pentaerythritol tetranitrate, PETN, C5H8N4O12) and a wide band gap aluminum oxide
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Optical absorption measurements are combined with electronic structure calculations to explore photochemistry of an α-Al2O3-PETN interface formed by a nitroester (pentaerythritol tetranitrate, PETN, C5H8N4O12) and a wide band gap aluminum oxide (α-Al2O3) substrate. The first principles modeling is used to deconstruct and interpret the α-Al2O3-PETN absorption spectrum that has distinct peaks attributed to surface F0-centers and surface—PETN transitions. We predict the low energy α-Al2O3 F0-center—PETN transition, producing the excited triplet state, and α-Al2O3 F0-center—PETN charge transfer, generating the PETN anion radical. This implies that irradiation by commonly used lasers can easily initiate photodecomposition of both excited and charged PETN at the interface. The feasible mechanism of the photodecomposition is proposed. Full article
(This article belongs to the Special Issue Photoactive Molecules)
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Open AccessArticle The Role of CD44 and ERM Proteins in Expression and Functionality of P-glycoprotein in Breast Cancer Cells
Molecules 2016, 21(3), 290; https://doi.org/10.3390/molecules21030290
Received: 16 December 2015 / Revised: 22 February 2016 / Accepted: 23 February 2016 / Published: 1 March 2016
Cited by 13 | PDF Full-text (2866 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and
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Multidrug resistance (MDR) is often attributed to the over-expression of P-glycoprotein (P-gp), which prevents the accumulation of anticancer drugs within cells by virtue of its active drug efflux capacity. We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and proposed the involvement of a unique protein complex in regulating this process. In this paper, we investigate the role of these mediators in the regulation of P-gp functionality and hence the acquisition of MDR following cell to cell transfer. By sequentially silencing the FERM domain-binding proteins, Ezrin, Radixin and Moesin (ERM), as well as CD44, which we also report a selective packaging in breast cancer derived EVs, we have established a role for these proteins, in particular Radixin and CD44, in influencing the P-gp-mediated MDR in whole cells. We also report for the first time the role of ERM proteins in the vesicular transfer of functional P-gp. Specifically, we demonstrate that intercellular membrane insertion is dependent on Ezrin and Moesin, whilst P-gp functionality is governed by the integrity of all ERM proteins in the recipient cell. This study identifies these candidate proteins as potential new therapeutic targets in circumventing MDR clinically. Full article
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)
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Open AccessArticle Modified Polyacrylic Acid-Zinc Composites: Synthesis, Characterization and Biological Activity
Molecules 2016, 21(3), 292; https://doi.org/10.3390/molecules21030292
Received: 6 January 2016 / Revised: 13 February 2016 / Accepted: 25 February 2016 / Published: 29 February 2016
PDF Full-text (4599 KB) | HTML Full-text | XML Full-text
Abstract
Polyacrylic acid (PAA) is an important industrial chemical, which has been extensively applied in various fields, including for several biomedical purposes. In this study, we report the synthesis and modification of this polymer with various phenol imides, such as succinimide, phthalimide and 1,8-naphthalimide.
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Polyacrylic acid (PAA) is an important industrial chemical, which has been extensively applied in various fields, including for several biomedical purposes. In this study, we report the synthesis and modification of this polymer with various phenol imides, such as succinimide, phthalimide and 1,8-naphthalimide. The as-synthesized derivatives were used to prepare polymer metal composites by the reaction with Zn+2. These composites were characterized by using various techniques, including NMR, FT-IR, TGA, SEM and DSC. The as-prepared PAA-based composites were further evaluated for their anti-microbial properties against various pathogens, which include both Gram-positive and Gram-negative bacteria and different fungal strains. The synthesized composites have displayed considerable biocidal properties, ranging from mild to moderate activities against different strains tested. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds
Molecules 2016, 21(3), 293; https://doi.org/10.3390/molecules21030293
Received: 18 January 2016 / Accepted: 25 February 2016 / Published: 14 March 2016
Cited by 10 | PDF Full-text (1208 KB) | HTML Full-text | XML Full-text
Abstract
The global burden of bacterial infections is very high and has been exacerbated by increasing resistance to multiple antibiotics. Antibiotic resistance leads to failed treatment of infections, which can ultimately lead to death. To overcome antibiotic resistance, it is necessary to identify new
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The global burden of bacterial infections is very high and has been exacerbated by increasing resistance to multiple antibiotics. Antibiotic resistance leads to failed treatment of infections, which can ultimately lead to death. To overcome antibiotic resistance, it is necessary to identify new antibacterial agents. In this study, a total of 662 plant extracts (diverse parts) from 222 plant species (82 families, 177 genera) were screened for antibacterial activity using the agar cup plate method. The aqueous and methanolic extracts were prepared from diverse plant parts and screened against eight bacterial (two Gram-positive and six Gram-negative) species, most of which are involved in common infections with multiple antibiotic resistance. The methanolic extracts of several plants were shown to have zones of inhibition ≥ 12 mm against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was calculated only with methanolic extracts of selected plants, those showed zone of inhibition ≥ 12 mm against both Gram-positive and Gram-negative bacteria. Several extracts had minimum inhibitory concentration ≤ 1 mg/mL. Specifically Adhatoda vasica, Ageratum conyzoides, Alangium salvifolium, Alpinia galanga, Andrographis paniculata, Anogeissus latifolia, Annona squamosa, A. reticulate, Azadirachta indica, Buchanania lanzan, Cassia fistula, Celastrus paniculatus, Centella asiatica, Clausena excavate, Cleome viscosa, Cleistanthus collinus, Clerodendrum indicum, Croton roxburghii, Diospyros melanoxylon, Eleutherine bulbosa, Erycibe paniculata, Eryngium foetidum, Garcinia cowa, Helicteres isora, Hemidesmus indicus, Holarrhena antidysenterica, Lannea coromandelica, Millettia extensa, Mimusops elengi, Nyctanthes arbor-tristis, Oroxylum indicum, Paederia foetida, Pterospermum acerifolium, Punica granatum, Semecarpus anacardium, Spondias pinnata, Terminalia alata and Vitex negundo were shown to have significant antimicrobial activity. The species listed here were shown to have anti-infective activity against both Gram-positive and Gram-negative bacteria. These results may serve as a guide for selecting plant species that could yield the highest probability of finding promising compounds responsible for the antibacterial activities against a broad spectrum of bacterial species. Further investigation of the phytochemicals from these plants will help to identify the lead compounds for drug discovery. Full article
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Open AccessArticle Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo
Molecules 2016, 21(3), 295; https://doi.org/10.3390/molecules21030295
Received: 7 January 2016 / Revised: 16 February 2016 / Accepted: 23 February 2016 / Published: 1 March 2016
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Abstract
Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects
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Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Optimization of Microwave-Assisted Extraction Conditions for Five Major Bioactive Compounds from Flos Sophorae Immaturus (Cultivars of Sophora japonica L.) Using Response Surface Methodology
Molecules 2016, 21(3), 296; https://doi.org/10.3390/molecules21030296
Received: 14 December 2015 / Revised: 22 February 2016 / Accepted: 23 February 2016 / Published: 2 March 2016
Cited by 6 | PDF Full-text (6069 KB) | HTML Full-text | XML Full-text
Abstract
Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design
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Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design was employed to optimize experimental conditions (liquid-to-solid ratio; microwave power; and extraction time) based on the results of single factor tests to extract the five major components in Flos Sophorae Immaturus. Experimental data were fitted to a second-order polynomial equation using multiple regression analysis. Data were also analyzed using appropriate statistical methods. Optimal extraction conditions were as follows: extraction solvent; 100% methanol; particle size; 100 mesh; extraction frequency; 1; liquid-to-solid ratio; 50:1; microwave power; 287 W; and extraction time; 80 s. A rapid and sensitive ultra-high performance liquid chromatography method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (EIS-Q-TOF MS/MS) was developed and validated for the simultaneous determination of rutin; quercetin; genistein; kaempferol; and isorhamnetin in Flos Sophorae Immaturus. Chromatographic separation was accomplished on a Kinetex C18 column (100 mm × 2.1 mm; 2.6 μm) at 40 °C within 5 min. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile (71:29; v/v). Isocratic elution was carried out at a flow rate of 0.35 mL/min. The constituents of Flos Sophorae Immaturus were simultaneously identified by EIS-Q-TOF MS/MS in multiple reaction monitoring mode. During quantitative analysis; all of the calibration curves showed good linear relationships (R2 > 0.999) within the tested ranges; and mean recoveries ranged from 96.0216% to 101.0601%. The precision determined through intra- and inter-day studies showed an RSD% of <2.833%. These results demonstrate that the developed method is accurate and effective and could be readily utilized for the comprehensive quality control of Flos Sophorae Immaturus. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells
Molecules 2016, 21(3), 297; https://doi.org/10.3390/molecules21030297
Received: 1 February 2016 / Revised: 25 February 2016 / Accepted: 26 February 2016 / Published: 2 March 2016
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Abstract
Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL), extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small
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Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL), extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways. Full article
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Open AccessArticle Rhubarb Anthraquinones Protect Rats against Mercuric Chloride (HgCl2)-Induced Acute Renal Failure
Molecules 2016, 21(3), 298; https://doi.org/10.3390/molecules21030298
Received: 18 January 2016 / Revised: 15 February 2016 / Accepted: 23 February 2016 / Published: 8 March 2016
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Abstract
Mercury (Hg) causes severe nephrotoxicity in subjects with excess exposure. This work attempted to identify whether a natural medicine—rhubarb—has protective effects against mercuric chloride (HgCl2)-induced acute renal failure (ARF), and which of its components contributed most to the treatment. Total rhubarb
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Mercury (Hg) causes severe nephrotoxicity in subjects with excess exposure. This work attempted to identify whether a natural medicine—rhubarb—has protective effects against mercuric chloride (HgCl2)-induced acute renal failure (ARF), and which of its components contributed most to the treatment. Total rhubarb extract (TR) were separated to the total anthraquinones (TA), the total tannins (TT) and remaining component extract (RC). Each extract was orally pre-administered to rats for five successive days followed by HgCl2 injection to induce kidney injury. Subsequently, renal histopathology and biochemical examinations were performed in vitro to evaluate the protective effects. Pharmacological studies showed that TR and TA, but not TT or RC manifested significant protection activity against HgCl2-induced ARF. There were also significant declines of serum creatine, urea nitrogen values and increases of total protein albumin levels in TR and TA treated groups compared to HgCl2 alone (p < 0.05). At last, the major components in TA extract were further identified as anthraquinones by liquid chromatography coupled mass spectroscopy. This study thus provides observational evidences that rhubarb could ameliorate HgCl2-induced ARF and its anthraquinones in particular are the effective components responsible for this activity in rhubarb extract. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of New Bis(3-hydroxy-4-pyridinone) Ligands as Chelating Agents for Uranyl Complexation
Molecules 2016, 21(3), 299; https://doi.org/10.3390/molecules21030299
Received: 22 January 2016 / Revised: 19 February 2016 / Accepted: 23 February 2016 / Published: 8 March 2016
PDF Full-text (815 KB) | HTML Full-text | XML Full-text
Abstract
Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by 1H-NMR, 13C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were
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Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by 1H-NMR, 13C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were also determined by UV spectrophotometry in aqueous media. Results showed that the efficiencies of these chelating agents are dependent on the linker length. Ligand 4b is the best chelator and suitable for further studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood–Brain Barrier in Vitro Model
Molecules 2016, 21(3), 300; https://doi.org/10.3390/molecules21030300
Received: 11 January 2016 / Revised: 24 February 2016 / Accepted: 25 February 2016 / Published: 2 March 2016
Cited by 3 | PDF Full-text (1512 KB) | HTML Full-text | XML Full-text
Abstract
The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood–brain barrier so
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The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood–brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10−6 to 0.705 × 10−6 cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na2 suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Achillolide A Protects Astrocytes against Oxidative Stress by Reducing Intracellular Reactive Oxygen Species and Interfering with Cell Signaling
Molecules 2016, 21(3), 301; https://doi.org/10.3390/molecules21030301
Received: 14 January 2016 / Revised: 23 February 2016 / Accepted: 25 February 2016 / Published: 2 March 2016
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Abstract
Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain
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Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain astrocytes (primary cultures) was determined by lactate dehydrogenase (LDH) activity, intracellular ROS levels were detected using 2′,7′-dichlorofluorescein diacetate, in vitro antioxidant activity was measured by differential pulse voltammetry, and protein phosphorylation was determined using specific ELISA kits. We have found that achillolide A prevented the H2O2-induced death of astrocytes, and attenuated the induced intracellular accumulation of reactive oxygen species (ROS). These activities could be attributed to the inhibition of the H2O2-induced phosphorylation of MAP/ERK kinase 1 (MEK1) and p44/42 mitogen-activated protein kinases (MAPK), and to the antioxidant activity of achillolide A, but not to H2O2 scavenging. This is the first study that demonstrates its protective effects on brain astrocytes, and its ability to interfere with MAPK activation. We propose that achillolide A deserves further evaluation for its potential to be developed as a drug for the prevention/treatment of neurodegenerative diseases and brain injuries where oxidative stress is part of the pathophysiology. Full article
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Open AccessArticle Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits
Molecules 2016, 21(3), 302; https://doi.org/10.3390/molecules21030302
Received: 24 January 2016 / Revised: 28 February 2016 / Accepted: 29 February 2016 / Published: 2 March 2016
Cited by 5 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text
Abstract
Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro.
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Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC50 value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells
Molecules 2016, 21(3), 306; https://doi.org/10.3390/molecules21030306
Received: 28 January 2016 / Revised: 24 February 2016 / Accepted: 26 February 2016 / Published: 3 March 2016
Cited by 6 | PDF Full-text (2248 KB) | HTML Full-text | XML Full-text
Abstract
Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well
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Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reaction
Molecules 2016, 21(3), 307; https://doi.org/10.3390/molecules21030307
Received: 16 January 2016 / Revised: 23 February 2016 / Accepted: 26 February 2016 / Published: 4 March 2016
Cited by 4 | PDF Full-text (2330 KB) | HTML Full-text | XML Full-text
Abstract
The CuI- or Ag2CO3-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a–d (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-ClC6H4) produces in good yields
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The CuI- or Ag2CO3-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a–d (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-ClC6H4) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a–d (Ar = Ph, p-MeC6H4, p-OMeC6H4, p-ClC6H4), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adducts 4 and 6. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by an X-ray diffraction study of 4a, and in the case of 6a by XH-correlation and HMBC spectra. Full article
(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)
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Open AccessArticle Casbane Diterpenes from Red Sea Coral Sinularia polydactyla
Molecules 2016, 21(3), 308; https://doi.org/10.3390/molecules21030308
Received: 11 February 2016 / Revised: 25 February 2016 / Accepted: 29 February 2016 / Published: 3 March 2016
Cited by 6 | PDF Full-text (1720 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O
[...] Read more.
The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4–5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans
Molecules 2016, 21(3), 309; https://doi.org/10.3390/molecules21030309
Received: 18 December 2015 / Revised: 22 February 2016 / Accepted: 24 February 2016 / Published: 4 March 2016
Cited by 5 | PDF Full-text (4312 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were
[...] Read more.
Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle bis-Nitrile and bis-Dialkylcyanamide Platinum(II) Complexes as Efficient Catalysts for Hydrosilylation Cross-Linking of Siloxane Polymers
Molecules 2016, 21(3), 311; https://doi.org/10.3390/molecules21030311
Received: 1 February 2016 / Revised: 29 February 2016 / Accepted: 1 March 2016 / Published: 5 March 2016
Cited by 4 | PDF Full-text (1353 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
cis- and trans-Isomers of the platinum(II) nitrile complexes [PtCl2(NCR)2] (R = NMe2, N(C5H10), Ph, CH2Ph) were examined as catalysts for hydrosilylation cross-linking of vinyl-terminated polydimethylsiloxane and trimethylsilyl-terminated poly(dimethylsiloxane-co
[...] Read more.
cis- and trans-Isomers of the platinum(II) nitrile complexes [PtCl2(NCR)2] (R = NMe2, N(C5H10), Ph, CH2Ph) were examined as catalysts for hydrosilylation cross-linking of vinyl-terminated polydimethylsiloxane and trimethylsilyl-terminated poly(dimethylsiloxane-co-ethylhydrosiloxane) producing high quality silicone rubbers. Among the tested platinum species the cis-complexes are much more active catalysts than their trans-congeners and for all studied platinum complexes cis-[PtCl2(NCCH2Ph)2] exhibits the best catalytic activity (room temperature, c = 1.0 × 10−4 mol/L, τpot-life 60 min, τcuring 6 h). Although cis-[PtCl2(NCCH2Ph)2] is less active than the widely used Karstedt’s catalyst, its application for the cross-linking can be performed not only at room temperature (c = 1.0 × 10−4 mol/L), but also, more efficiently, at 80 °C (c = 1.0 × 10−4–1.0 × 10−5 mol/L) and it prevents adherence of the formed silicone rubbers to equipment. The usage of the cis- and trans-[PtCl2(NCR)2] complexes as the hydrosilylation catalysts do not require any inhibitors and, moreover, the complexes and their mixtures with vinyl- and trimethylsilyl terminated polysiloxanes are shelf-stable in air. Tested catalysts do not form colloid platinum particles after the cross-linking. Full article
(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)
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Open AccessArticle Synthesis, Characterization and in Vitro Evaluation of Manganese Ferrite (MnFe2O4) Nanoparticles for Their Biocompatibility with Murine Breast Cancer Cells (4T1)
Molecules 2016, 21(3), 312; https://doi.org/10.3390/molecules21030312
Received: 24 December 2015 / Revised: 23 February 2016 / Accepted: 24 February 2016 / Published: 11 March 2016
Cited by 6 | PDF Full-text (1897 KB) | HTML Full-text | XML Full-text
Abstract
Manganese ferrite (MnFe2O4) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform
[...] Read more.
Manganese ferrite (MnFe2O4) magnetic nanoparticles were successfully prepared by a sol-gel self-combustion technique using iron nitrate and manganese nitrate, followed by calcination at 150 °C for 24 h. Calcined sample was systematically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrational sample magnetometry (VSM) in order to identify the crystalline phase, functional group, morphology, particle size, shape and magnetic behavior. It was observed that the resultant spinal ferrites obtained at low temperature exhibit single phase, nanoparticle size and good magnetic behavior. The study results have revealed the existence of a potent dose dependent cytotoxic effect of MnFe2O4 nanoparticles against 4T1 cell lines at varying concentrations with IC50 values of 210, 198 and 171 μg/mL after 24 h, 48 h and 72 h of incubation, respectively. Cells exposed to higher concentrations of nanoparticles showed a progressive increase of apoptotic and necrotic activity. Below 125 μg/mL concentration the nanoparticles were biocompatible with 4T1 cells. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
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Open AccessArticle Inulin and Fibersol-2 Combined Have Hypolipidemic Effects on High Cholesterol Diet-Induced Hyperlipidemia in Hamsters
Molecules 2016, 21(3), 313; https://doi.org/10.3390/molecules21030313
Received: 23 January 2016 / Revised: 1 March 2016 / Accepted: 2 March 2016 / Published: 5 March 2016
Cited by 4 | PDF Full-text (4479 KB) | HTML Full-text | XML Full-text
Abstract
The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin
[...] Read more.
The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin to assess a pooled effect on modulation of hyperlipidemia. We aimed to investigate the effects of this combined supplement (defined as InF) on hamsters fed a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet, HCD) to induce hyperlipidemia. A total of 40 male hamsters were randomly assigned to five groups (n = 8 per group) for treatment: standard diet, vehicle (control); or vehicle or InF supplementation by oral gavage at 0, 864, 1727, or 2591 mg/kg/day for eight weeks, designated HCD, InF-1X, InF-2X, and InF-3X groups, respectively. The hypolipidemic efficacy and safety of InF supplementation was assessed by serum lipid indexes, hepatic and fecal lipid content, and histology. InF supplementation significantly improved serum levels of triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) and the ratio of LDL-C/HDL-C after two-week treatment, and reduced serum total cholesterol (TC) levels after four-week administration. After eight-week supplementation, InF supplementation dose-dependently improved serum levels of TC, TG, HDL-C, and LDL-C; LDL-C/HDL-C ratio; and hepatic TC and TG levels. It inhibited TC absorption by feces elimination. Our study provides experiment-based evidence to support that this prebiotics remedy may be useful in preventing or treating hyperlipidemia. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Isolation, Purification and Quantification of Ginsenoside F5 and F3 Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng
Molecules 2016, 21(3), 315; https://doi.org/10.3390/molecules21030315
Received: 26 December 2015 / Revised: 24 February 2016 / Accepted: 3 March 2016 / Published: 9 March 2016
Cited by 3 | PDF Full-text (1885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, the isolation, purification and quantification of ginsenoside F5 and F3 isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at
[...] Read more.
In this paper, the isolation, purification and quantification of ginsenoside F5 and F3 isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at analytical scale was achieved using a Zorbax Eclipse XDB C-18 column with a ternary mobile phase of acetonitrile–water–phosphoric acid (28:71:1) at a flow rate of 1.0 mL/min within 40 min. UV detection was set at 203 nm. Ginsenoside F5 and F3 was 4.21 mg and 5.13 mg in 1 g flower buds of P. ginseng (FBPG), respectively. The preparation of ginsenoside F5 and F3 at semi-preparative scale was performed by using a Daisogel C-18 column and gradient elution system of acetonitrile–water (32:68 → 28:72) at a flow rate of 10 mL/min with a sample load of 20–30 mg, and yielded ginsenosides in purity of more than 96%. Their structures were characterized by NMR and high resolution electrospray ionization mass spectrometry (HRESIMS). All the method validations showed acceptable limits. The results indicate a new source to obtain ginsenoside F5 and F3, and show that the method developed here appears to be reliable for simultaneously preparing them from CEFBPG. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile
Molecules 2016, 21(3), 316; https://doi.org/10.3390/molecules21030316
Received: 24 January 2016 / Revised: 28 February 2016 / Accepted: 2 March 2016 / Published: 8 March 2016
Cited by 3 | PDF Full-text (3302 KB) | HTML Full-text | XML Full-text
Abstract
Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants.
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Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant. Full article
(This article belongs to the Special Issue Biosynthesis of Natural Products)
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Open AccessArticle Pharmacokinetic-Pharmacodynamic Modeling to Study the Antipyretic Effect of Qingkailing Injection on Pyrexia Model Rats
Molecules 2016, 21(3), 317; https://doi.org/10.3390/molecules21030317
Received: 4 January 2016 / Revised: 26 February 2016 / Accepted: 26 February 2016 / Published: 7 March 2016
Cited by 5 | PDF Full-text (13344 KB) | HTML Full-text | XML Full-text
Abstract
Qingkailing injection (QKLI) is a modern Chinese medicine preparation derived from a well-known classical formulation, An-Gong-Niu-Huang Wan. Although the clinical efficacy of QKLI has been well defined, its severe adverse drug reactions (ADRs) were extensively increased. Through thorough attempts to reduce ADR rates,
[...] Read more.
Qingkailing injection (QKLI) is a modern Chinese medicine preparation derived from a well-known classical formulation, An-Gong-Niu-Huang Wan. Although the clinical efficacy of QKLI has been well defined, its severe adverse drug reactions (ADRs) were extensively increased. Through thorough attempts to reduce ADR rates, it was realized that the effect-based rational use plays the key role in clinical practices. Hence, the pharmacokinetic-pharmacodynamic (PK-PD) model was introduced in the present study, aiming to link the pharmacokinetic profiles with the therapeutic outcomes of QKLI, and subsequently to provide valuable guidelines for the rational use of QKLI in clinical settings. The PK properties of the six dominant ingredients in QKLI were compared between the normal treated group (NTG) and the pyrexia model group (MTG). Rectal temperatures were measured in parallel with blood sampling for NTG, MTG, model control group (MCG), and normal control group (NCG). Baicalin and geniposide exhibited appropriate PK parameters, and were selected as the PK markers to map the antipyretic effect of QKLI. Then, a PK-PD model was constructed upon the bacalin and geniposide plasma concentrations vs. the rectal temperature variation values, by a two-compartment PK model with a Sigmoid Emax PD model to explain the time delay between the drug plasma concentration of PK markers and the antipyretic effect after a single dose administration of QKLI. The findings obtained would provide fundamental information to propose a more reasonable dosage regimen and improve the level of individualized drug therapy in clinical settings. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core
Molecules 2016, 21(3), 318; https://doi.org/10.3390/molecules21030318
Received: 9 February 2016 / Accepted: 24 February 2016 / Published: 7 March 2016
Cited by 6 | PDF Full-text (1518 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress
[...] Read more.
Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds. Full article
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
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Open AccessArticle Differential Response of Two Human Breast Cancer Cell Lines to the Phenolic Extract from Flaxseed Oil
Molecules 2016, 21(3), 319; https://doi.org/10.3390/molecules21030319
Received: 30 January 2016 / Revised: 26 February 2016 / Accepted: 2 March 2016 / Published: 8 March 2016
Cited by 4 | PDF Full-text (1376 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous
[...] Read more.
Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Liquid Chromatography with Tandem Mass Spectrometry: A Sensitive Method for the Determination of Dehydrodiisoeugenol in Rat Cerebral Nuclei
Molecules 2016, 21(3), 321; https://doi.org/10.3390/molecules21030321
Received: 24 January 2016 / Revised: 26 February 2016 / Accepted: 1 March 2016 / Published: 9 March 2016
PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C18 column with methanol–water containing 0.1% formic
[...] Read more.
A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C18 column with methanol–water containing 0.1% formic acid (81:19, v/v) as a mobile phase. Detection of DDIE was performed on a positive electrospray ionization source using a triple quadrupole mass spectrometer. DDIE and daidzein were monitored at m/z 327.2→188.0 and m/z 255.0→199.2, respectively, in multiple reaction monitoring mode. This method enabled quantification of DDIE in various brain areas, including, cortex, hippocampus, striatum, hypothalamus, cerebellum and brainstem, with high specificity, precision, accuracy, and recovery. The data herein demonstrate that our new LC-MS/MS method is highly sensitive and suitable for monitoring cerebral nuclei distribution of DDIE. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Proteomic Profiling of Iron Overload-Induced Human Hepatic Cells Reveals Activation of TLR2-Mediated Inflammatory Response
Molecules 2016, 21(3), 322; https://doi.org/10.3390/molecules21030322
Received: 25 January 2016 / Revised: 29 February 2016 / Accepted: 2 March 2016 / Published: 17 March 2016
Cited by 2 | PDF Full-text (1999 KB) | HTML Full-text | XML Full-text
Abstract
Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially
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Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle New Cerebroside and Nucleoside Derivatives from a Red Sea Strain of the Marine Cyanobacterium Moorea producens
Molecules 2016, 21(3), 324; https://doi.org/10.3390/molecules21030324
Received: 16 January 2016 / Revised: 1 March 2016 / Accepted: 1 March 2016 / Published: 9 March 2016
Cited by 3 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3),
[...] Read more.
In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1–5 showed variable cytotoxic activity against three cancer cell lines. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage
Molecules 2016, 21(3), 325; https://doi.org/10.3390/molecules21030325
Received: 5 January 2016 / Revised: 24 February 2016 / Accepted: 2 March 2016 / Published: 10 March 2016
Cited by 7 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel
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Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Hydrazonoyl Chlorides as Precursors for Synthesis of Novel Bis-Pyrrole Derivatives
Molecules 2016, 21(3), 326; https://doi.org/10.3390/molecules21030326
Received: 30 January 2016 / Revised: 29 February 2016 / Accepted: 29 February 2016 / Published: 9 March 2016
Cited by 3 | PDF Full-text (3531 KB) | HTML Full-text | XML Full-text
Abstract
A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular
[...] Read more.
A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular docking of the bis-pyrrole derivatives was performed by the Molecular Operating Environment (MOE) program. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle A Computational Study of the Mechanism of Succinimide Formation in the Asn–His Sequence: Intramolecular Catalysis by the His Side Chain
Molecules 2016, 21(3), 327; https://doi.org/10.3390/molecules21030327
Received: 30 January 2016 / Revised: 3 March 2016 / Accepted: 4 March 2016 / Published: 9 March 2016
Cited by 3 | PDF Full-text (1127 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of
[...] Read more.
The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of the succinimide intermediate is by far the fastest when Xxx is glycine (Gly), the smallest amino acid residue, while extremely slow when Xxx is bulky such as isoleucine (Ile) and valine (Val). In this respect, it is very interesting to note that the succinimide formation is definitely accelerated when Xxx is histidine (His) despite its large size. In this paper, we computationally show that, in an Asn–His sequence, the His side-chain imidazole group (in the neutral Nε-protonated form) can specifically catalyze the formation of the tetrahedral intermediate in the succinimide formation by mediating a proton transfer. The calculations were performed for Ace−Asn−His−Nme (Ace = acetyl, Nme = methylamino) as a model compound by the density functional theory with the B3LYP functional and the 6-31+G(d,p) basis set. We also show that the tetrahedral intermediate, once protonated at the NH2 group, easily releases an ammonia molecule to give the succinimide species. Full article
(This article belongs to the Special Issue Biomolecules Modification)
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Open AccessArticle Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate
Molecules 2016, 21(3), 328; https://doi.org/10.3390/molecules21030328
Received: 18 January 2016 / Revised: 5 February 2016 / Accepted: 23 February 2016 / Published: 9 March 2016
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Abstract
Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the
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Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures. Full article
(This article belongs to the Special Issue Crystallization of Pharmaceuticals)
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Open AccessArticle Synthesis and Selective Cytotoxic Activities on Rhabdomyosarcoma and Noncancerous Cells of Some Heterocyclic Chalcones
Molecules 2016, 21(3), 329; https://doi.org/10.3390/molecules21030329
Received: 20 January 2016 / Revised: 1 March 2016 / Accepted: 3 March 2016 / Published: 9 March 2016
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Abstract
Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on
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Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1. Full article
(This article belongs to the Special Issue ECSOC-19)
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Open AccessArticle Investigation of the Pyridinium Ylide—Alkyne Cycloaddition as a Fluorogenic Coupling Reaction
Molecules 2016, 21(3), 332; https://doi.org/10.3390/molecules21030332
Received: 26 January 2016 / Revised: 3 March 2016 / Accepted: 4 March 2016 / Published: 10 March 2016
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Abstract
The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied,
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The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate
Molecules 2016, 21(3), 333; https://doi.org/10.3390/molecules21030333
Received: 24 December 2015 / Revised: 23 February 2016 / Accepted: 26 February 2016 / Published: 10 March 2016
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Abstract
Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in
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Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in methanol led to transesterification instead of the alkylation, while the use of NaOEt led to low yields of the N-alkylated acids. Hydrazinolysis of the ester gave indol-2-carbohydrazide which then was allowed to react with different aromatic aldehydes and ke