Molecules

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Open AccessArticle

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

by Željka Babić, Maja Crkvenčić, Zrinka Rajić, Ana-Matea Mikecin, Marijeta Kralj, Jan Balzarini, Mariya Petrova, Jos Vanderleyden and Branka Zorc

Molecules 2012, 17(1), 1124-1137; https://doi.org/10.3390/molecules17011124 - 23 Jan 2012

Cited by 13 | Viewed by 9194

Abstract

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes [...] Read more.

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC₅₀ = 1-4.3 μmol·L⁻¹). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Phenolic Enriched Extract of Baccharis trimera Presents Anti-inflammatory and Antioxidant Activities

by Cristiane B. De Oliveira, Lucimara N. Comunello, Adroaldo Lunardelli, Robson H. Amaral, Melissa G. S. Pires, Gabriela Lucas Da Silva, Vanusa Manfredini, Carmen Regla Vargas, Simone C. B. Gnoatto, Jarbas R. De Oliveira and Grace Gosmann

Molecules 2012, 17(1), 1113-1123; https://doi.org/10.3390/molecules17011113 - 23 Jan 2012

Cited by 43 | Viewed by 9194

Abstract

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) [...] Read more.

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group ( p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity ( p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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324 KiB

Open AccessCommunication

The Newly Isolated Endophytic Fungus Paraconiothyrium sp. LK1 Produces Ascotoxin

by Abdul Latif Khan, Muhammad Hamayun, Javid Hussain, Sang-Mo Kang and In-Jung Lee

Molecules 2012, 17(1), 1103-1112; https://doi.org/10.3390/molecules17011103 - 20 Jan 2012

Cited by 30 | Viewed by 6760

Abstract

We have isolated five endophytic fungi from the roots of Capsicum annuum, Cucumis sativus and Glycine max. The culture filtrates (CF) of these endophytes were screened on dwarf mutant rice (Waito-C) and normal rice (Dongjin-byeo). Endophyte CAC-1A significantly inhibited [...] Read more.

We have isolated five endophytic fungi from the roots of Capsicum annuum, Cucumis sativus and Glycine max. The culture filtrates (CF) of these endophytes were screened on dwarf mutant rice (Waito-C) and normal rice (Dongjin-byeo). Endophyte CAC-1A significantly inhibited the growth of Waito-C and Dongjin-byeo. Endophyte CAC-1A was identified as Paraconiothyrium sp. by sequencing the ITS rDNA region and phylogenetic analysis. The ethyl acetate fraction of Paraconiothyrium sp. suppressed the germination of Lactuca sativa and Echinochloa crus-galli seeds. The ethyl acetate fraction of the endophyte was subjected to bioassay-guided isolation and we obtained the phytotoxic compound ascotoxin (1) which was characterized through NMR and GC/MS techniques. Ascotoxin revealed 100% inhibitory effects on seed germination of Echinochloa crus-galli. Compound (1) was isolated for the first time from Paraconiothyrium sp. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Diversity Oriented Syntheses of Conventional Heterocycles by Smart Multi Component Reactions (MCRs) of the Last Decade

by Heiner Eckert

Molecules 2012, 17(1), 1074-1102; https://doi.org/10.3390/molecules17011074 - 20 Jan 2012

Cited by 156 | Viewed by 11780

Abstract

A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will provide a high degree of applying economical and ecological advantages as well as [...] Read more.

A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will provide a high degree of applying economical and ecological advantages as well as of practicability. Water, ionic liquids, and solvent-less syntheses as well as use of various forms of energy as microwave and ultrasonic irradiation are examined and discussed. Full article

(This article belongs to the Special Issue Multicomponent Reaction)

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Open AccessArticle

Fluorescent Lipids: Functional Parts of Fusogenic Liposomes and Tools for Cell Membrane Labeling and Visualization

by Christian Kleusch, Nils Hersch, Bernd Hoffmann, Rudolf Merkel and Agnes Csiszár

Molecules 2012, 17(1), 1055-1073; https://doi.org/10.3390/molecules17011055 - 20 Jan 2012

Cited by 75 | Viewed by 14421

Abstract

In this paper a rapid and highly efficient method for controlled incorporation of fluorescent lipids into living mammalian cells is introduced. Here, the fluorescent molecules have two consecutive functions: First, they trigger rapid membrane fusion between cellular plasma membranes and the lipid bilayers [...] Read more.

In this paper a rapid and highly efficient method for controlled incorporation of fluorescent lipids into living mammalian cells is introduced. Here, the fluorescent molecules have two consecutive functions: First, they trigger rapid membrane fusion between cellular plasma membranes and the lipid bilayers of their carrier particles, so called fusogenic liposomes, and second, after insertion into cellular membranes these molecules enable fluorescence imaging of cell membranes and membrane traffic processes. We tested the fluorescent derivatives of the following essential membrane lipids for membrane fusion: Ceramide, sphingomyelin, phosphocholine, phosphatidylinositol-bisphosphate, ganglioside, cholesterol, and cholesteryl ester. Our results show that all probed lipids could more efficiently be incorporated into the plasma membrane of living cells than by using other methods. Moreover, labeling occurred in a gentle manner under classical cell culture conditions reducing cellular stress responses. Staining procedures were monitored by fluorescence microscopy and it was observed that sphingolipids and cholesterol containing free hydroxyl groups exhibit a decreased distribution velocity as well as a longer persistence in the plasma membrane compared to lipids without hydroxyl groups like phospholipids or other artificial lipid analogs. After membrane staining, the fluorescent molecules were sorted into membranes of cell organelles according to their chemical properties and biological functions without any influence of the delivery system. Full article

(This article belongs to the Special Issue Fluorophores - The Fluorescent Toolbox in Biological and Biomedical Research)

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Open AccessArticle

The Metal Cation Chelating Capacity of Astaxanthin. Does This Have Any Influence on Antiradical Activity?

by Elizabeth Hernández-Marin, Andrés Barbosa and Ana Martínez

Molecules 2012, 17(1), 1039-1054; https://doi.org/10.3390/molecules17011039 - 20 Jan 2012

Cited by 40 | Viewed by 8478

Abstract

In this Density Functional Theory study, it became apparent that astaxanthin (ASTA) may form metal ion complexes with metal cations such as Ca⁺², Cu⁺², Pb⁺², Zn⁺², Cd⁺² and Hg⁺². The presence of [...] Read more.

In this Density Functional Theory study, it became apparent that astaxanthin (ASTA) may form metal ion complexes with metal cations such as Ca⁺², Cu⁺², Pb⁺², Zn⁺², Cd⁺² and Hg⁺². The presence of metal cations induces changes in the maximum absorption bands which are red shifted in all cases. Therefore, in the case of compounds where metal ions are interacting with ASTA, they are redder in color. Moreover, the antiradical capacity of some ASTA-metal cationic complexes was studied by assessing their vertical ionization energy and vertical electron affinity, reaching the conclusion that metal complexes are slightly better electron donors and better electron acceptors than ASTA. Full article

(This article belongs to the Special Issue Carotenoids)

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Open AccessArticle

Synthesis and Preliminary Antimicrobial Activities of New Arylideneamino-1,3,4-thiadiazole-(thio/dithio)-acetamido Cephalosporanic Acids

by Shakir Mahmood Alwan

Molecules 2012, 17(1), 1025-1038; https://doi.org/10.3390/molecules17011025 - 19 Jan 2012

Cited by 27 | Viewed by 6668

Abstract

New derivatives of 7-aminocephalosporanic acid 1–8 were synthesized by acylation of the 7-amino group of the cephem nucleus with various arylidinimino-1,3,4-thiadiazole-thio(or dithio)-acetic acid intermediates 3a–d and 5a–d, respectively, so the acyl side chains of these new [...] Read more.

New derivatives of 7-aminocephalosporanic acid 1–8 were synthesized by acylation of the 7-amino group of the cephem nucleus with various arylidinimino-1,3,4-thiadiazole-thio(or dithio)-acetic acid intermediates 3a–d and 5a–d, respectively, so the acyl side chains of these new cephalosporins contained a sulfide or disulfide bond. This unique combination of a Schiff base with the sulfide or disulfide bonds in the acyl side chain afforded new cephalosporins of reasonable potencies, some of which were found to possess moderate activities against the tested microorganisms. Their chemical structures were characterized by ¹H-NMR, IR spectroscopy and elemental microanalysis. Preliminary in vitro antimicrobial activities of the prepared cephalosporins were investigated using a panel of selected microorganisms. Results indicated that the newly synthesized cephalosporins containing disulfide bonds (compounds 5–8) exhibited better activities against Staphylococcus aureus and Escherichia coli. The cephalosporins cross-linked by a sulfide bond (compounds 1–4) showed a slight change in antimicrobial activities when compared with that of the reference cephalosporin (cephalexin). Full article

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Open AccessArticle

Antifungal Activity of Eugenol Analogues. Influence of Different Substituents and Studies on Mechanism of Action

by Héctor Carrasco, Marcela Raimondi, Laura Svetaz, Melina Di Liberto, María V. Rodriguez, Luis Espinoza, Alejandro Madrid and Susana Zacchino

Molecules 2012, 17(1), 1002-1024; https://doi.org/10.3390/molecules17011002 - 19 Jan 2012

Cited by 97 | Viewed by 10330

Abstract

Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence [...] Read more.

Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH₃ at C-2 or the presence of one or two NO₂ groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL⁻¹. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity. Full article

(This article belongs to the Special Issue Dendrimers - from Synthesis to Applications)

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Open AccessArticle

Synthesis, Structure and Antifungal Activity of New 3-[(5-Aryl-1,3,4-oxadiazol-2-yl)methyl]benzo[d]thiazol-2(3H)-ones

by Jian-Quan Weng, Xing-Hai Liu, Hua Huang, Cheng-Xia Tan and Jie Chen

Molecules 2012, 17(1), 989-1001; https://doi.org/10.3390/molecules17010989 - 18 Jan 2012

Cited by 19 | Viewed by 6444

Abstract

A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl₃ under reflux conditions. The structures of the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR, MS and elemental analysis. [...] Read more.

A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl₃ under reflux conditions. The structures of the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR, MS and elemental analysis. Furthermore, the structure of compound 4i was determined by single-crystal X-ray diffraction. The preliminary bioassy results indicated that some of them showed moderate inhibition activity against Colletotrichum orbiculare, Botrytis cinerea and Rhizoctonia solani. Full article

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Open AccessArticle

Synthesis, Reactions and Antimicrobial Activities of 8-Ethoxycoumarin Derivatives

by Hany M. Mohamed, Ashraf H. F. Abd El-Wahab, Kamal A. Ahmed, Ahmed M. El-Agrody, Ahmed H. Bedair, Fathy A. Eid and Mostafa M. Khafagy

Molecules 2012, 17(1), 971-988; https://doi.org/10.3390/molecules17010971 - 18 Jan 2012

Cited by 38 | Viewed by 8416

Abstract

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl₃ gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c [...] Read more.

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl₃ gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH₂)₂·H₂O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a–c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity. Full article

(This article belongs to the Special Issue Heterocycles)

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Open AccessArticle

Effect of Wine and Vinegar Processing of Rhizoma Corydalis on the Tissue Distribution of Tetrahydropalmatine, Protopine and Dehydrocorydaline in Rats

by Zhiying Dou, Kefeng Li, Ping Wang and Liu Cao

Molecules 2012, 17(1), 951-970; https://doi.org/10.3390/molecules17010951 - 18 Jan 2012

Cited by 21 | Viewed by 6704

Abstract

Vinegar and wine processing of medicinal plants are two traditional pharmaceutical techniques which have been used for thousands of years in China. Tetrahydropalmatine (THP), dehydrocorydaline (DHC) and protopine are three major bioactive molecules in Rhizoma Corydalis. In this study, a simple and reliable [...] Read more.

Vinegar and wine processing of medicinal plants are two traditional pharmaceutical techniques which have been used for thousands of years in China. Tetrahydropalmatine (THP), dehydrocorydaline (DHC) and protopine are three major bioactive molecules in Rhizoma Corydalis. In this study, a simple and reliable HPLC method was developed for simultaneous analysis of THP, DHC and protopine in rat tissues after gastric gavage administration of Rhizoma Corydalis. The validated HPLC method was successfully applied to investigate the effect of wine and vinegar processing on the compounds’ distribution in rat tissues. Our results showed that processing mainly affect the T_max and mean residence time (MRT) of the molecules without changing their C_max and AUC_0–24_h Vinegar processing significantly increased the T_max of DHC in heart, kidney, cerebrum, cerebrellum, brain stem and striatum and prolonged the T_max of protopine in brain. No significant changes were observed on the T_max of THP in rat tissues after vinegar processing. Wine processing reduced the T_max of protopine and DHC in liver and spleen and T_max of protopine in lung, but increased the T_max of THP in all the rat tissues examined. To our knowledge, this is the first report on the effects of processing on the tissue distribution of the bioactive molecules from Rhizoma Corydalis. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Antioxidant Effect of Stryphnodendron rotundifolium Martius Extracts from Cariri-Ceará State (Brazil): Potential Involvement in Its Therapeutic Use

by José Galberto Martins da Costa, Gerlânia de Oliveira Leite, Albys Ferrer Dubois, Rodrigo Lopes Seeger, Aline Augusti Boligon, Margareth Linde Athayde, Adriana Rolim Campos and João Batista Teixeira da Rocha

Molecules 2012, 17(1), 934-950; https://doi.org/10.3390/molecules17010934 - 18 Jan 2012

Cited by 21 | Viewed by 6575

Abstract

Stryphnodendron rotundifolium is a phytotherapic used in the northeast of Brazil for the treatment of inflammatory processes which normally are associated with oxidative stress. Consequently, we have tested the antioxidant properties of hydroalcoholic (HAB) and aqueous extracts (AB) from the bark and aqueous [...] Read more.

Stryphnodendron rotundifolium is a phytotherapic used in the northeast of Brazil for the treatment of inflammatory processes which normally are associated with oxidative stress. Consequently, we have tested the antioxidant properties of hydroalcoholic (HAB) and aqueous extracts (AB) from the bark and aqueous extract (AL) from the leaves of Stryphnodendron rotundifolium to determine a possible association between antioxidant activity and the popular use of this plant. Free radical scavenger properties were assessed by the quenching of 1′,1′-diphenil-2-picrylhydrazyl (DPPH) and the calculated IC₅₀ were: HAB = 5.4 ± 0.7, AB = 12.0 ± 2.6, and AL = 46.3 ± 12.3 µg/mL. Total phenolic contents were: HAB = 102.7 ± 2.8, AB = 114.4 ± 14.6, and AL = 93.8 ± 9.1 µg/mg plant). HPLC/DAD analyses indicated that gallic acid, catechin, rutin and caffeic acid were the major components of the crude extracts of S. rotundifolium. Plant extracts inhibited Fe(II)-induced lipid peroxidation in brain homogenates. Iron chelation was also investigated and only HBA exhibited a weak activity. Taken together, the results suggest that S. rotundifolium could be considered an effective agent in the prevention of diseases associated with oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Oligothiophenes as Fluorescent Markers for Biological Applications

by Massimo L. Capobianco, Giovanna Barbarella and Antonio Manetto

Molecules 2012, 17(1), 910-933; https://doi.org/10.3390/molecules17010910 - 18 Jan 2012

Cited by 45 | Viewed by 8330

Abstract

This paper summarizes some of our results on the application of oligothiophenes as fluorescent markers for biological studies. The oligomers of thiophene, widely known for their semiconductor properties in organic electronics, are also fluorescent compounds characterized by chemical and optical stability, high absorbance [...] Read more.

This paper summarizes some of our results on the application of oligothiophenes as fluorescent markers for biological studies. The oligomers of thiophene, widely known for their semiconductor properties in organic electronics, are also fluorescent compounds characterized by chemical and optical stability, high absorbance and quantum yield. Their fluorescent emission can be easily modulated via organic synthesis by changing the number of thiophene rings and the nature of side-chains. This review shows how oligothiophenes can be derivatized with active groups such as phosphoramidite, N-hydroxysuccinimidyl and 4-sulfotetrafluorophenyl esters, isothiocyanate and azide by which the (bio)molecules of interest can be covalently bound. This paper also describes how molecules such as oligonucleotides, proteins and even nanoparticles, tagged with oligothiophenes, can be used in experiments ranging from hybridization studies to imaging of fixed and living cells. Finally, a few multilabeling experiments are described. Full article

(This article belongs to the Special Issue Fluorophores - The Fluorescent Toolbox in Biological and Biomedical Research)

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Open AccessArticle

Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines

by Hamad M. Al-Matar, Khaled D. Khalil, Mona F. Al-Kanderi and Mohamed H. Elnagdi

Molecules 2012, 17(1), 897-909; https://doi.org/10.3390/molecules17010897 - 18 Jan 2012

Cited by 11 | Viewed by 6891

Abstract

3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N [...] Read more.

3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N-methyl-benzimidazole with the cyanoanhydride formed by condensation of cyanoacetic acid with acetic anhydride, leads to the formation of 2-(1,3-diacetyl-2,3-dihydro-1H-benzo[d]-imidazol-2-yl)acetonitrile (5), whose structure was confirmed by X-ray crystallographic analysis. 3-Oxoalkanenitriles 3a,b were observed to undergo condensation reactions with dimethylformamide dimethyl acetal (DMFDMA) to afford the corresponding enamino-nitriles, which react with malononitrile to give 2-dialkylaminopyridines through a pathway involving a new, unexpected rearrangement process. Reactions of 3-oxoalkanenitriles with ethyl acetoacetate were found to afford 2-oxopyran-3-carbonitriles, also occurring via this unexpected rearrangement process. Mechanisms to account for both rearrangement reactions are suggested. In addition, reactions of 3-oxoalkanenitriles with acetylacetone in acetic acid in the presence of ammonium acetate result in the formation of pyridine-3-carbonitriles. Finally, upon heating in the presence of zeolite 3-oxoalkanenitriles 3b,c self-trimerized to produce the corresponding aniline derivatives 23b,c. Full article

(This article belongs to the Special Issue Heterocycles)

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Open AccessArticle

Design, Synthesis and Antifibrotic Activities of Carbohydrate- Modified 1-(Substituted aryl)-5-trifluoromethyl-2(1H) Pyridones

by Qinghua Lou, Xiangbao Meng, Zhiqi Lao, Lingling Xuan, Jinye Bai, Qi Hou, Gaoyun Hu, Renna Luo, Lijian Tao and Zhongjun Li

Molecules 2012, 17(1), 884-896; https://doi.org/10.3390/molecules17010884 - 17 Jan 2012

Cited by 20 | Viewed by 7074

Abstract

Pirfenidone, a pyridone compound, is an effective and novel antifibrotic agent. In this article, we describe the design, synthesis and activity evaluation of novel antifibrotic agents, 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones modified with carbohydrate. Most of the title compounds exhibited comparable or better [...] Read more.

Pirfenidone, a pyridone compound, is an effective and novel antifibrotic agent. In this article, we describe the design, synthesis and activity evaluation of novel antifibrotic agents, 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones modified with carbohydrate. Most of the title compounds exhibited comparable or better inhibitory activity than fluorofenidone. Notably, compound 19a demonstrated the highest cell-based inhibitory activity against NIH 3T3 (IC₅₀ = 0.17 mM). Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Novel Benzothiazole, Benzimidazole and Benzoxazole Derivatives as Potential Antitumor Agents: Synthesis and Preliminary in Vitro Biological Evaluation

by Pu Xiang, Tian Zhou, Liang Wang, Chang-Yan Sun, Jing Hu, Ying-Lan Zhao and Li Yang

Molecules 2012, 17(1), 873-883; https://doi.org/10.3390/molecules17010873 - 17 Jan 2012

Cited by 78 | Viewed by 10595

Abstract

In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through [...] Read more.

In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue 1d showed comparable antiproliferative activity in vitro with better solubility, compared with 1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded 1f and 1g, whose activities were fundamentally retained. In the preliminary in vitro biological evaluation, the immunofluorescence staining of HCT116 cells indicated that 1d, 1f and 1g led to cytosolic vacuolization which was not induced by 1a at low micromolecular concentrations. These results suggest that these optimized compounds might potentially constitute a novel class of anticancer agents, which merit further studies. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Phytochemical Study and Anti-inflammatory, Antidiabetic and Free Radical Scavenger Evaluations of Krameria pauciflora Methanol Extract

by M. Ángeles Ramírez-Cisneros, María Yolanda Rios, Myrna Déciga-Campos and A. Berenice Aguilar-Guadarrama

Molecules 2012, 17(1), 861-872; https://doi.org/10.3390/molecules17010861 - 17 Jan 2012

Cited by 11 | Viewed by 7339

Abstract

The plant Krameria pauciflora MOC et. Sessé ex DC. is used as an anti-inflammatory and antidiabetic in traditional medicine. The aim of this study was to evaluate the in vivo anti-inflammatory and antidiabetic effects of a methanol extract from the roots of K. [...] Read more.

The plant Krameria pauciflora MOC et. Sessé ex DC. is used as an anti-inflammatory and antidiabetic in traditional medicine. The aim of this study was to evaluate the in vivo anti-inflammatory and antidiabetic effects of a methanol extract from the roots of K. pauciflora. Dichloromethane and ethyl acetate extracts obtained by partitioning the methanol extract were also evaluated. Complete methanol and dichloromethane extracts showed anti-inflammatory effects at 3 mg/kg. An anti-inflammatory effect similar to indomethacin (10 mg/kg) was observed when the methanol and dichloromethane extracts, which contain a cycloartane-type triterpene and an sterol, were administered orally at several doses (3, 10, 30 and 100 mg/kg), whereas no anti-inflammatory effect was observed at any dose for the ethyl acetate extract, which contains catechin-type flavonoids. The antidiabetic effect of each extract was also determined. An antihyperglycaemic effect was observed in diabetic rats, but no effect in normoglycaemic animals was observed when the methanol extract was administrated at 30 mg/kg. All of the extracts exhibited radical scavenger activity. Additionally, constituents from all of the extracts were identified by NMR. This article supports the use of K. pauciflora as an anti-inflammatory because it exhibits a similar effect to indomethacin. However, its antidiabetic effect is not completely clear, although it could be useful for preventing diabetic complications. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Effect of Efavirenz on UDP-Glucuronosyltransferase 1A1, 1A4, 1A6, and 1A9 Activities in Human Liver Microsomes

by Hye Young Ji, Hyeri Lee, Sae Rom Lim, Jeong Han Kim and Hye Suk Lee

Molecules 2012, 17(1), 851-860; https://doi.org/10.3390/molecules17010851 - 17 Jan 2012

Cited by 21 | Viewed by 6317

Abstract

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used for the treatment of human immunodeficiency virus type 1 infections. Drug interactions of efavirenz have been reported due to in vitro inhibition of CYP2C9, CYP2C19, CYP3A4, and UDP-glucuronosyltransferase 2B7 (UGT2B7) and in vivo CYP3A4 induction. [...] Read more.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used for the treatment of human immunodeficiency virus type 1 infections. Drug interactions of efavirenz have been reported due to in vitro inhibition of CYP2C9, CYP2C19, CYP3A4, and UDP-glucuronosyltransferase 2B7 (UGT2B7) and in vivo CYP3A4 induction. The inhibitory potentials of efavirenz on the enzyme activities of four major UDP-glucuronosyltransferases (UGTs), 1A1, 1A4, 1A6, and 1A9, in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Efavirenz potently inhibited UGT1A4-mediated trifluoperazine N-glucuronidation and UGT1A9-mediated propofol glucuronidation, with K_i values of 2.0 and 9.4 μM, respectively. [I]/K_i ratios of efavirenz for trifluoperazine N-glucuronidation and propofol glucuronidation were 6.5 and 1.37, respectively. Efavirenz also moderately inhibited UGT1A1-mediated 17β-estradiol 3-glucuronidation, with a K_i value of 40.3 μM, but did not inhibit UGT1A6-mediated 1-naphthol glucuronidation. Those in vitro results suggest that efavirenz should be examined for potential pharmacokinetic drug interactions in vivo due to strong inhibition of UGT1A4 and UGT1A9. Full article

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Open AccessArticle

Two Novel Naphthalene Glucosides and an Anthraquinone Isolated from Rumex dentatus and Their Antiproliferation Activities in Four Cell Lines

by Hui Zhang, Zengjun Guo, Nan Wu, Wenming Xu, Ling Han, Nan Li and Yanxia Han

Molecules 2012, 17(1), 843-850; https://doi.org/10.3390/molecules17010843 - 17 Jan 2012

Cited by 79 | Viewed by 7337

Abstract

An ethyl acetate extract of the roots of Rumex dentatus L. was investigated. Three compounds were identified by their spectroscopic data as chrysophanol (1), 6-methyl-7-acetyl-1, 8-dihydroxy-3-methoxy naphthalene-1-O-β-D(L)-glucoside (2) and 6-methyl-7-acetyl-1, 8-dihydroxy naphthalene-1-O-β-D(L)-glucoside (3) [...] Read more.

An ethyl acetate extract of the roots of Rumex dentatus L. was investigated. Three compounds were identified by their spectroscopic data as chrysophanol (1), 6-methyl-7-acetyl-1, 8-dihydroxy-3-methoxy naphthalene-1-O-β-D(L)-glucoside (2) and 6-methyl-7-acetyl-1, 8-dihydroxy naphthalene-1-O-β-D(L)-glucoside (3) were found in the plant for the first time. Compounds 2 and 3 are novel compounds. Their antiproliferation activities were tested by the MTT assay in four cell lines (breast cancer MCF-7, gastric cancer 7901, melanoma A375 and oophoroma SKOV-3). Full article

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Open AccessArticle

Isostreptazolin and Sannaphenol, Two New Metabolites from Streptomyces sannanensis

by Dan Zheng, Li Han, Yiqing Li, Jun Li, He Rong, Qiao Leng, Yi Jiang, Lixing Zhao and Xueshi Huang

Molecules 2012, 17(1), 836-842; https://doi.org/10.3390/molecules17010836 - 16 Jan 2012

Cited by 14 | Viewed by 4933

Abstract

Two new compounds, isostreptazolin (1) and sannaphenol (2), were isolated from the culture broth of Streptomyces sannanensis and their structures elucidated on the basis of 1D and 2D NMR as well as MS, IR and UV spectroscopic data analysis. [...] Read more.

Two new compounds, isostreptazolin (1) and sannaphenol (2), were isolated from the culture broth of Streptomyces sannanensis and their structures elucidated on the basis of 1D and 2D NMR as well as MS, IR and UV spectroscopic data analysis. The cytotoxic activity of 1 and 2 were evaluated. Both compounds were inactive against H460 and HeLa cell lines at 100 mM. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine

by Aslan M. Esmurziev, Arne Reimers, Trygve Andreassen, Nebojsa Simic, Eirik Sundby and Bård Helge Hoff

Molecules 2012, 17(1), 820-835; https://doi.org/10.3390/molecules17010820 - 16 Jan 2012

Cited by 3 | Viewed by 8347

Abstract

A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri- [...] Read more.

A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri-O-benzoyl-α-D-glycopyranosyl bromide)uronate proceeded to give the N2-conjugate. However, lamotrigine-N2-glucuronide was most efficiently synthesised from methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromide)uronate. Employing nitromethane as solvent with CdCO₃ as a base lamotrigine-N2 glucuronide was prepared in a high yield (41%). Also methyl (2,3-di-O-benzoyl-4-deoxy-4-fluoro-α-D-glucosyl bromide)uronate underwent N-glucuronidation, but the product was unstable, eliminating hydrogen fluoride to give the corresponding enoate conjugate. Full article

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Open AccessArticle

Comparative Computational Studies of 3,4-Dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile Derivatives as Potential Antinociceptive Agents

by Janaína V. dos Anjos, Rajendra M. Srivastava, João H. Costa-Silva, Luciana Scotti, Marcus T. Scotti, Almir G. Wanderley, Elisa Soares Leite, Sebastião J. de Melo and Francisco J. B. Mendonça Junior

Molecules 2012, 17(1), 809-819; https://doi.org/10.3390/molecules17010809 - 16 Jan 2012

Cited by 20 | Viewed by 6086

Abstract

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a–i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information [...] Read more.

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a–i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series. Full article

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Open AccessArticle

Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice

by Weiming Xu, Lizhi Liu, Nicola J. Brown, Sven Christian and David Hornby

Molecules 2012, 17(1), 796-808; https://doi.org/10.3390/molecules17010796 - 16 Jan 2012

Cited by 37 | Viewed by 9162

Abstract

Semiconductor quantum dots (Qdots) have recently been shown to offer significant advantages over conventional fluorescent probes to image and study biological processes. The stability and low toxicity of QDs are well suited for biological applications. Despite this, the potential of Qdots remains limited [...] Read more.

Semiconductor quantum dots (Qdots) have recently been shown to offer significant advantages over conventional fluorescent probes to image and study biological processes. The stability and low toxicity of QDs are well suited for biological applications. Despite this, the potential of Qdots remains limited owing to the inefficiency of existing delivery methods. By conjugating Qdots with small antibody fragments targeting membrane-bound proteins, such as GRP78, we demonstrate here that the Quantum dot- Anti-GRP78 scFv (Qdot-GRP78) retains its immunospecificity and its distribution can be monitored by visualization of multi-color fluorescence imaging both in vitro and in vivo. Moreover we demonstrate here for the first time that Qdot-GRP78 scFv bioconjugates can be efficiently internalized by cancer cells, thus upregulate phophosphate-AKT-ser473 and possess biological anti-tumour activity as shown by inhibition of breast cancer growth in a xenograft model. This suggests that nanocarrier-conjugated scFvs can be used as a therapeutic antibody for cancer treatment. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase

by Ines Primožič, Marijana Bolant, Alma Ramić and Srđanka Tomić

Molecules 2012, 17(1), 786-795; https://doi.org/10.3390/molecules17010786 - 16 Jan 2012

Cited by 4 | Viewed by 6171

Abstract

Since the optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds, a new biocatalytic method for the production of chiral quinuclidin-3-ols was examined. Butyrylcholinesterase (BChE; EC 3.1.1.8) was chosen as a biocatalyst in a preparative kinetic [...] Read more.

Since the optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds, a new biocatalytic method for the production of chiral quinuclidin-3-ols was examined. Butyrylcholinesterase (BChE; EC 3.1.1.8) was chosen as a biocatalyst in a preparative kinetic resolution of enantiomers. A series of racemic, (R)- and (S)-esters of quinuclidin-3-ol and acetic, benzoic, phthalic and isonicotinic acids were synthesized, as well as their racemic quaternary N-benzyl, meta- and para-N-bromo and N-methylbenzyl derivatives. After the resolution, all N-benzyl protected groups were successfully removed by catalytic transfer hydrogenation with ammonium formate (10% Pd-C). Hydrolyses studies with BChE confirmed that (R)-enantiomers of the prepared esters are much better substrates for the enzyme than (S)-enantiomers. Introduction of bromine atom or methyl group in the meta or para position of the benzyl moiety resulted in a considerable improvement of the stereoselectivity compared to the non-substituted compounds. Optically pure quinuclidin-3-ols were prepared in high yields and enantiopurity by the usage of various N-benzyl protected groups and BChE as a biocatalyst. Full article

(This article belongs to the Special Issue ECSOC-15)

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Open AccessArticle

Anti-bacterial Treatment of Polyethylene by Cold Plasma for Medical Purposes

by Anton Popelka, Igor Novák, Marián Lehocký, Ivan Chodák, Ján Sedliačik, Milada Gajtanska, Mariana Sedliačiková, Alenka Vesel, Ita Junkar, Angela Kleinová, Milena Špírková and František Bílek

Molecules 2012, 17(1), 762-785; https://doi.org/10.3390/molecules17010762 - 13 Jan 2012

Cited by 57 | Viewed by 8504

Abstract

Polyethylene (PE) is one of the most widely used polymers in many industrial applications. Biomedical uses seem to be attractive, with increasing interest. However, PE it prone to infections and its additional surface treatment is indispensable. An increase in resistance to infections can [...] Read more.

Polyethylene (PE) is one of the most widely used polymers in many industrial applications. Biomedical uses seem to be attractive, with increasing interest. However, PE it prone to infections and its additional surface treatment is indispensable. An increase in resistance to infections can be achieved by treating PE surfaces with substances containing antibacterial groups such as triclosan (5-Chloro-2-(2,4-dichlorophenoxy)phenol) and chlorhexidine (1,1'-Hexamethylenebis[5-(4-chlorophenyl)biguanide]). This work has examined the impact of selected antibacterial substances immobilized on low-density polyethylene (LDPE) via polyacrylic acid (PAA) grafted on LDPE by low-temperature barrier discharge plasma. This LDPE surface treatment led to inhibition of Escherichia coli and Staphylococcus aureus adhesion; the first causes intestinal disease, peritonitis, mastitis, pneumonia, septicemia, the latter is the reason for wound and urinary tract infections. Full article

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Open AccessArticle

Isolation and Structural Characterisation of Okara Polysaccharides

by Bo Li, Fei Lu, Haijuan Nan and Yang Liu

Molecules 2012, 17(1), 753-761; https://doi.org/10.3390/molecules17010753 - 13 Jan 2012

Cited by 44 | Viewed by 8779

Abstract

Okara is a byproduct generated during tofu or soymilk production processes. Crude polysaccharide (yield 56.8%) was isolated by removing fat, protein and low molecular weight carbohydrates from initial okara. Crude okara polysaccharide was further divided into four soluble fractions and an insoluble residue [...] Read more.

Okara is a byproduct generated during tofu or soymilk production processes. Crude polysaccharide (yield 56.8%) was isolated by removing fat, protein and low molecular weight carbohydrates from initial okara. Crude okara polysaccharide was further divided into four soluble fractions and an insoluble residue fraction by extracting with 0.05 M EDTA + NH₄ oxalate, 0.05 M NaOH, 1 M NaOH and 4 M NaOH, with yields of 7.7%, 3.6%, 20.7%, 16.0% and 27.9%, respectively. Arabinose, galactose, galacturonic acid, xylose and glucose (only for the insoluble fraction) were the major constituent sugars. The primary sugar residues of okara polysaccharides were 1,4-linked β-galactopyranose, 1,5- and 1,3-linked α-arabinofuranose, 1,5-linked α-xylofuranose, 1,2-linked, 1,2,4-linked and terminal α-rhamnopyranose (or fucopyranose), and 1,4-linked β-glucopyranose (only for the insoluble fraction), indicating okara polysaccharides might contain galactan, arabinan, arabinogalactan, xylogalacturonan, rhamnogalacturonan, xylan, xyloglucan and cellulose. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

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Open AccessArticle

Comparison of Polysaccharides from Two Species of Ganoderma

by Jing Xie, Jing Zhao, De-Jun Hu, Jin-Ao Duan, Yu-Ping Tang and Shao-Ping Li

Molecules 2012, 17(1), 740-752; https://doi.org/10.3390/molecules17010740 - 13 Jan 2012

Cited by 54 | Viewed by 8490

Abstract

Ganoderma lucidum and Ganoderma sinense, known as Lingzhi in Chinese, are commonly used Chinese medicines with excellent beneficial health effects. Triterpenes and polysaccharides are usually considered as their main active components. However, the content of triterpenes differs significantly between the two species [...] Read more.

Ganoderma lucidum and Ganoderma sinense, known as Lingzhi in Chinese, are commonly used Chinese medicines with excellent beneficial health effects. Triterpenes and polysaccharides are usually considered as their main active components. However, the content of triterpenes differs significantly between the two species of Ganoderma. To date, a careful comparison of polysaccharides from the two species of Ganoderma has not been performed. In this study, polysaccharides from fruiting bodies of two species of Lingzhi collected from different regions of China were analyzed and compared based on HPSEC-ELSD and HPSEC-MALLS-RI analyses, as well as enzymatic digestion and HPTLC of acid hydrolysates. The results indicated that both the HPSEC-ELSD profiles and the molecular weights of the polysaccharides were similar. Enzymatic digestion showed that polyshaccharides from all samples of Lingzhi could be hydrolyzed by pectinase and dextranase. HPTLC profiles of their TFA hydrolysates colored with different reagents and their monosaccharides composition were also similar. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

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Open AccessArticle

Reaction Characteristics of Andrographolide and its Analogue AL-1 with GSH, as a Simple Chemical Simulation of NF-κB Inhibition

by Hui Yao, Sha Li, Pei Yu, Xiaodan Tang, Jie Jiang and Yuqiang Wang

Molecules 2012, 17(1), 728-739; https://doi.org/10.3390/molecules17010728 - 12 Jan 2012

Cited by 12 | Viewed by 5728

Abstract

14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In [...] Read more.

14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro. Full article

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Open AccessArticle

Evaluation of the Immunity Activity of Glycyrrhizin in AR Mice

by Xiao-Lan Li and Ai-Guo Zhou

Molecules 2012, 17(1), 716-727; https://doi.org/10.3390/molecules17010716 - 12 Jan 2012

Cited by 39 | Viewed by 6197

Abstract

In this study, we evaluated effect of glycyrrhizin on immunity function in allergic rhinitis (AR) mice. The AR mice model were induced by dripping ovalbumin in physiological saline (2 mg mL⁻¹, 10 μL) into the bilateral nasal cavities using a micropipette. [...] Read more.

In this study, we evaluated effect of glycyrrhizin on immunity function in allergic rhinitis (AR) mice. The AR mice model were induced by dripping ovalbumin in physiological saline (2 mg mL⁻¹, 10 μL) into the bilateral nasal cavities using a micropipette. After the AR model was induced, mice were randomly divided into six groups: the normal control, model, lycopene 20 mg kg⁻¹ (as positive control drug) group, and glycyrrhizin 10, 20, 30 mg kg⁻¹ groups. After the sensitization day 14, lycopene (20 mg/kg BW) and glycyrrhizin (10, 20 and 30 mg/kg BW) were given orally for 20 days once a day. Mice in the normal control and model groups were given saline orally once a day for 20 days. Results showed that glycyrrhizin treatment could dose-dependently significantly reduce blood immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), nitrous oxide (NO), tumor necrosis factor-alpha (TNF-α) levels and nitrous oxide synthase (NOS) activity and enhance blood immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-2 (IL-2) and interleukin-12 (IL-12) levels in AR mice. Furthermore, glycyrrhizin treatment could dose-dependently significantly enhance acetylcholinesterase (AchE) activity and reduce substance P (SP) level in peripheral blood and nasal mucosa of AR mice. We conclude that glycyrrhizin can improve immunity function in AR mice, suggesting a potential drug for the prevention and therapy of AR. Full article

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Open AccessArticle

Controlled Fabrication of Flower-like Nickel Oxide Hierarchical Structures and Their Application in Water Treatment

by Feifei Tao, Yongmiao Shen and Linxia Wang

Molecules 2012, 17(1), 703-715; https://doi.org/10.3390/molecules17010703 - 12 Jan 2012

Cited by 25 | Viewed by 6612

Abstract

Flower-like NiO hierarchical structures with 2–5 μm diameter assembled from nanosheet building blocks have been successfully fabricated via a wet-chemical method combined with thermodecomposition technology. The template-free method is facile and effective in preparing flower-like NiO superstructures in high yield. The intermediate product [...] Read more.

Flower-like NiO hierarchical structures with 2–5 μm diameter assembled from nanosheet building blocks have been successfully fabricated via a wet-chemical method combined with thermodecomposition technology. The template-free method is facile and effective in preparing flower-like NiO superstructures in high yield. The intermediate product and final hierarchical structures are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform IR (FTIR), and thermogravimetric analysis (TGA). The effects of growth temperature and reaction time on the morphologies of the as-prepared structures were investigated by SEM characterization and a possible mechanism for the formation of flower-like NiO is proposed. Based on the nitrogen adsorption and desorption measurements, the BET surface area of the as-obtained sample is 55.7 m²/g and the pore-size distribution plot indicates a bimodal mesopore distribution, with pore sizes of ca. 2.6 nm and 7.4 nm, respectively. In comparison with sphere-like and rod-like structures, the flower-like NiO hierarchical structures show an excellent ability to rapidly remove various pollutants when used as adsorbent and photocatalyst in waste-water treatment, which may be attributed to its unique hierarchical and porous surface structures. Full article

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Molecules, Volume 17, Issue 1 (January 2012) – 76 articles , Pages 1-1137

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