Molecules

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Open AccessArticle

Synthesis of 1α,25-Dihydroxyvitamin D Analogues Featuring a S₂-symmetric CD-ring Core

by Garrett Minne, Lieve Verlinden, Annemieke Verstuyf and Pierre J. De Clercq

Molecules 2009, 14(2), 894-903; https://doi.org/10.3390/molecules14020894 - 24 Feb 2009

Cited by 7 | Viewed by 8950

Three analogues of 1a,25-dihydroxyvitamin D₃ (calcitriol), featuring a trans-fused decalin C,D-core with local S₂-symmetry, and possessing identical side-chain and seco-B,A-ring structures, have been synthesized starting from readily available (4aR,8aS)-octahydronaphthalene-1,5-dione (7). The very short sequences involve [...] Read more.

Three analogues of 1a,25-dihydroxyvitamin D₃ (calcitriol), featuring a trans-fused decalin C,D-core with local S₂-symmetry, and possessing identical side-chain and seco-B,A-ring structures, have been synthesized starting from readily available (4aR,8aS)-octahydronaphthalene-1,5-dione (7). The very short sequences involve the simultaneous introduction of the side-chain and seco-B,A-ring fragments via Suzuki and Sonogashira coupling reactions. The analogues are devoid of relevant biological activity. Full article

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Open AccessCorrection

Correction: Gruia, M.-I. et al. The Antioxidant Response Induced by Lonicera caerulaea Berry Extracts in Animals Bearing Experimental Solid Tumors. Molecules 2008, 13, 1195-1206

by Maria Iuliana Gruia, Eliza Oprea, Ion Gruia, Valentina Negoita and Ileana Cornelia Farcasanu

Molecules 2009, 14(2), 893; https://doi.org/10.3390/molecules14020893 - 24 Feb 2009

Cited by 5 | Viewed by 9086

Abstract

In the original published version of this paper [1] we omitted to acknowledge that the work was supported by a grant-in-aid. The acknowledgment is hereby published as follows. [...] Full article

399 KiB

Open AccessArticle

The X-Ray Crystal Structures of Primary Aryl Substituted Selenoamides

by Yang Li, Guo-Xiong Hua, Alexandra M. Z. Slawin and J. Derek Woollins

Molecules 2009, 14(2), 884-892; https://doi.org/10.3390/molecules14020884 - 23 Feb 2009

Cited by 18 | Viewed by 9469

Abstract

The X-ray structures of 12 primary selenoamides are reported. Metric parameters are provided, together with an illustration of the range of hydrogen bonding motifs. Full article

(This article belongs to the Special Issue Selenium and Tellurium Chemistry)

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312 KiB

Open AccessArticle

Design, Synthesis and Anti-HIV Integrase Evaluation of 4-Oxo-4H-quinolizine-3-carboxylic Acid Derivatives

by Yi-Sheng Xu, Cheng-Chu Zeng, Zi-Guo Jiao, Li-Ming Hu and Ru-gang Zhong

Molecules 2009, 14(2), 868-883; https://doi.org/10.3390/molecules14020868 - 19 Feb 2009

Cited by 43 | Viewed by 12176

Abstract

4-Oxo-4H-quinolizine-3-carboxylic acid derivatives bearing sulfamido, carboxylamido, benzimidazole and benzothiazole substituents have been designed and synthesized. The structures of these new compounds were confirmed by ¹H-NMR, ¹³C- NMR, IR and ESI (or HRMS) spectra. Compounds were screened for possible HIV integrase inhibitory activity. Full article

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281 KiB

Open AccessArticle

Bioactive Metabolites from Spilanthes acmella Murr.

by Supaluk Prachayasittikul, Saowapa Suphapong, Apilak Worachartcheewan, Ratana Lawung, Somsak Ruchirawat and Virapong Prachayasittikul

Molecules 2009, 14(2), 850-867; https://doi.org/10.3390/molecules14020850 - 19 Feb 2009

Cited by 236 | Viewed by 24573

Abstract

Spilanthes acmella Murr. (Compositae) has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains [...] Read more.

Spilanthes acmella Murr. (Compositae) has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains of microorganisms were performed. Results showed that fractions from the chloroform and methanol extracts inhibited the growth of many tested organisms, e.g. Corynebacterium diphtheriae NCTC 10356 with minimum inhibitory concentration (MIC) of 64-256 mg/mL and Bacillus subtilis ATCC 6633 with MIC of 128-256 mg/mL. The tested fractions all exhibited antioxidant properties in both DPPH and SOD assays. Potent radical scavenging activity was observed in the DPPH assay. No cytotoxic effects of the extracts against KB and HuCCA-1 cell lines were evident. Bioassay-guided isolation resulted in a diverse group of bioactive compounds such as phenolics [vanillic acid (2), trans-ferulic acid (5) and trans-isoferulic acid (6)], coumarin (scopoletin, 4) and triterpenoids like 3-acetylaleuritolic acid (1), b-sitostenone (3), stigmasterol and stigmasteryl-3-O-b-D-glucopyranosides, in addition to a mixture of stigmasteryl-and b-sitosteryl-3-O-b-D-glucopyranosides. The compounds 1–6 represent bioactive metabolites of S. acmella Murr. that were never previously reported. Our findings demonstrate for the first time the potential benefits of this medicinal plant as a rich source of high therapeutic value compounds for medicines, cosmetics, supplements and as a health food. Full article

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Open AccessArticle

High Quality Bergamot Oil from Greece: Chemical Analysis Using Chiral Gas Chromatography and Larvicidal Activity against the West Nile Virus Vector

by Melliou Eleni, Michaelakis Antonios, Koliopoulos George, Skaltsounis Alexios-Leandros and Magiatis Prokopios

Molecules 2009, 14(2), 839-849; https://doi.org/10.3390/molecules14020839 - 18 Feb 2009

Cited by 43 | Viewed by 16882 | Correction

Abstract

Τhe essential oils contained in the rind of the fruit and the leaves of bergamot from Greece (Citrus aurantium subsp. bergamia) were studied. The bergamot trees in question were cultivated on Kefalonia Island. The plant material (leaves and fruits in different [...] Read more.

Τhe essential oils contained in the rind of the fruit and the leaves of bergamot from Greece (Citrus aurantium subsp. bergamia) were studied. The bergamot trees in question were cultivated on Kefalonia Island. The plant material (leaves and fruits in different stages of maturity) was collected between December and March for a two year period. The rind of the fruit was separated manually and the essential oil was obtained either by cold pressing or by hydrodistillation. The maximum yield calculated on a wet weight of fresh rinds basis was 1.8%. The essential oils were first analyzed by GC-MS with a DB-5 column and then with a β-Dex™ enantiomeric column. The main constituent of the cold pressed essential oil of the rind was (–)-linalyl acetate with optical purity >99.9%. Other important constituents were (–)-linalool, (+)-limonene and γ-terpinene. The best value of linalool/linalyl acetate ratio was 0.38 and the maximum sum of linalool+linalyl acetate was found to be 55.8%. The larvacidal activities of the obtained essential oils and the compounds (±)-linalyl acetate, (±)-linalool and (–)-linalool were evaluated against larvae of the mosquito species Culex pipiens (Diptera: Culicidae), the West Nile virus vector, under laboratory conditions. The cold pressed essential oil showed an LC₅₀ value of 58 mg/L, while the LC₅₀ value of the corresponding essential oil obtained by hydrostillation was 106 mg/L. The essential oil of the leaves presented similar larvicidal toxicity with the cold pressed oil of the rind (LC₅₀=68 mg/L). Full article

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204 KiB

Open AccessArticle

Comparison of Phenolic Acids and Flavan-3-ols During Wine Fermentation of Grapes with Different Harvest Times

by Rong-Rong Tian, Qiu-Hong Pan, Ji-Cheng Zhan, Jing-Ming Li, Si-Bao Wan, Qing-Hua Zhang and Wei-Dong Huang

Molecules 2009, 14(2), 827-838; https://doi.org/10.3390/molecules14020827 - 18 Feb 2009

Cited by 69 | Viewed by 17882

Abstract

To explore the effects of harvest time on phenolic compounds during wine fermentation, grape berries (Vitis vinifera L. cv. Vidal) were harvested at 17.5, 22.8 and 37.2º Brix and were used to make dry wine, semi-sweet wine and icewine with low alcohol [...] Read more.

To explore the effects of harvest time on phenolic compounds during wine fermentation, grape berries (Vitis vinifera L. cv. Vidal) were harvested at 17.5, 22.8 and 37.2º Brix and were used to make dry wine, semi-sweet wine and icewine with low alcohol levels, respectively. Phenolic acids and flavan-3-ols were assayed during the fermentation of wines by means of reverse phase-high performance liquid chromatography (RP-HPLC). The results showed that concentrations of most of the phenolic acids and flavan-3-ol in musts increased with harvest time delay and higher total levels of these species were detected in all wines, compared with those measured before fermentation (the total phenolic acid content in wines was 1.5-2.0 fold that of in musts). Except for p-coumaric acid and (-)-epicatechin, other phenolic acids and flavan-3-ols had similar variation patterns (wave-like rise) during fermentation in dry wine and semi-sweet wine. However, some detected compounds, including gentisic acid, p-hydroxybenzoic acid, caffeic acid, p-coumaric acid and sinapic acid showed obviously different trends from the other two wines in the icewine making process. It is thus suggested that the harvest time has a decisive effect on phenols in final wines and influences the evolution of phenolic acids and flavan-3-ols during wine fermentation. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics)

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135 KiB

Open AccessArticle

Antioxidant Effects of Some Drugs on Ethanol-induced Ulcers

by Mira Popovic, Snezana Janicijevic-Hudomal, Biljana Kaurinovic, Julijana Rasic and Svetlana Trivic

Molecules 2009, 14(2), 816-826; https://doi.org/10.3390/molecules14020816 - 18 Feb 2009

Cited by 11 | Viewed by 8653

Abstract

The aim of this work was to investigate the antioxidant potential of some commonly used drugs (bromocriptine, haloperidol and azithromycin) on alcohol-induced ulcers in the rat. The following parameters were determined: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione reductase, glutathione [...] Read more.

The aim of this work was to investigate the antioxidant potential of some commonly used drugs (bromocriptine, haloperidol and azithromycin) on alcohol-induced ulcers in the rat. The following parameters were determined: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione reductase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity. A battery of biochemical assays were used and the resulting data was statistically analyzed. Alcohol stress caused gastric ulcerations and hemorrhages and changed all the examined parameters except glutathione peroxidase activity. All drugs reduced the ulcer index and hemorrhages, with azithromycin showing the strongest effects. The drugs in combination with alcohol showed different effects on biochemical parameters. Our results indicate that the gastroprotective effects of the investigated drugs on experimental lesions induced by 100% ethanol could not be correlated with their antioxidative properties. Full article

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Open AccessArticle

A Convenient Synthesis of Type A Procyanidins

by George A. Kraus, Yi Yuan and Aaron Kempema

Molecules 2009, 14(2), 807-815; https://doi.org/10.3390/molecules14020807 - 17 Feb 2009

Cited by 23 | Viewed by 10416

Abstract

Type A procyanidins can be synthesized in good yields from the condensation of benzopyrilium salts 8 and either catechin or phloroglucinol. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics)

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Open AccessArticle

Polyfunctional Nitriles in Organic Syntheses: A Novel Route to Aminopyrroles, Pyridazines and Pyrazolo[3,4-c]pyridazines

by Saleh M. Al-Mousawi, Moustafa Sherief Moustafa, Herbert Meier, Heinz Kolshorn and Mohamed Hilmy Elnagdi

Molecules 2009, 14(2), 798-806; https://doi.org/10.3390/molecules14020798 - 16 Feb 2009

Cited by 29 | Viewed by 11574

Abstract

Phenacylmalononitrile 1 reacts with dimethylformamide dimethyl acetal to yield an enaminone which could be readily converted into a pyrrole or an aminopyridazine by treating with ammonium acetate and hydrazine hydrate, respectively. Compound 1 reacted with hydrazine hydrate in ethanol at room temperature to [...] Read more.

Phenacylmalononitrile 1 reacts with dimethylformamide dimethyl acetal to yield an enaminone which could be readily converted into a pyrrole or an aminopyridazine by treating with ammonium acetate and hydrazine hydrate, respectively. Compound 1 reacted with hydrazine hydrate in ethanol at room temperature to yield the dihydropyridazine 9 as a single product. In refluxing ethanol this product further reacted with hydrazine hydrate to yield the novel dihydropyrazolopyridazinamine 10. Full article

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235 KiB

Open AccessArticle

2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation

by Jin Zhu, Tong Chen, Jie Liu, Ruoqun Ma, Weiqiang Lu, Jin Huang, Honglin Li, Jian Li and Hualiang Jiang

Molecules 2009, 14(2), 785-797; https://doi.org/10.3390/molecules14020785 - 16 Feb 2009

Cited by 15 | Viewed by 13564

Abstract

The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs. In this study, a series of novel small molecule FP-2 [...] Read more.

The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on compound 1, which was identified by using structure-based virtual screening in conjunction with an enzyme inhibition assay. All compounds showed high inhibitory effect against FP-2 with IC₅₀s of 1.46-11.38 μM, and the inhibitory activity of compound 2a was ~2 times greater than that of prototype compound 1. The preliminary SARs are summarized and should be helpful for future inhibitor design, and the novel scaffold presented here, with its potent inhibitory activity against FP-2, also has potential application in discovery of new anti-malarial drugs. Full article

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Open AccessArticle

Methyl Carbonium Ion Migration during the Reaction of 4-Chloro-5-methoxyl-3(2H)-pyridazinone with Trifluoroethylation Agents

by Qin Li, Guichun Lin, Li Liu, Zhenjun Yang and Li-He Zhang

Molecules 2009, 14(2), 777-784; https://doi.org/10.3390/molecules14020777 - 13 Feb 2009

Cited by 5 | Viewed by 11142

Abstract

To synthesize 4-chloro-5-methoxy-2-(b-trifluoroethyl)-3(2H)-pyridazinone (4), the reactions of 4-chloro-5-methoxy-3(2H)-pyridazinone (5) with RCH₂CF₃(R = I, TsO, MsO, TfO) in different solvents were studied. It was found that methyl group migration took place during this reaction. An oxonium [...] Read more.

To synthesize 4-chloro-5-methoxy-2-(b-trifluoroethyl)-3(2H)-pyridazinone (4), the reactions of 4-chloro-5-methoxy-3(2H)-pyridazinone (5) with RCH₂CF₃(R = I, TsO, MsO, TfO) in different solvents were studied. It was found that methyl group migration took place during this reaction. An oxonium salt 9 was suggested as the active intermediate for the formation of the byproduct4-chloro-5-methoxy-2-methyl-3(2H)-pyridazinone (7) and 4-chloro-2-methyl-5-(b-trifluoroethoxy)-3(2)-pyridazinone(8). Full article

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Open AccessArticle

A New O-Terpenoidal Coumarin from Clausena anisum-olens Merr.

by Yun-Song Wang, Hong-Yi Xu, Da-Xiang Wang and Jing-Hua Yang

Molecules 2009, 14(2), 771-776; https://doi.org/10.3390/molecules14020771 - 13 Feb 2009

Cited by 9 | Viewed by 13067

Abstract

A new O-terpenoidal coumarin 1, named hekumarone, was isolated from the leaves and twigs of Clausena anisum-olens Merr.(Rutaceae) collected in Hekou County in Yunnan Province, P. R. China. Structure elucidation and unambiguous NMR assignments for the title compound was carried out on [...] Read more.

A new O-terpenoidal coumarin 1, named hekumarone, was isolated from the leaves and twigs of Clausena anisum-olens Merr.(Rutaceae) collected in Hekou County in Yunnan Province, P. R. China. Structure elucidation and unambiguous NMR assignments for the title compound was carried out on the basis of 1D and 2D NMR experiments. Full article

(This article belongs to the Special Issue Coumarins and Xanthones)

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168 KiB

Open AccessArticle

Copper(II) Sulfamate: An Efficient Catalyst for the One-Pot Synthesis of 3,4-Dihydropyrimidine-2(1H)-ones and thiones

by Chen-Jiang Liu and Ji-De Wang

Molecules 2009, 14(2), 763-770; https://doi.org/10.3390/molecules14020763 - 13 Feb 2009

Cited by 77 | Viewed by 13369

Abstract

A simple, efficient procedure for the one-pot Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea employing copper(II) sulfamate as a novel catalyst is described. Compared to the classical Biginelli reaction conditions, the present method has the advantages of good yields, [...] Read more.

A simple, efficient procedure for the one-pot Biginelli condensation reaction of aldehydes, β-ketoesters and urea or thiourea employing copper(II) sulfamate as a novel catalyst is described. Compared to the classical Biginelli reaction conditions, the present method has the advantages of good yields, short reaction times and experimental simplicity. Full article

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Open AccessCommunication

Properties of an Oral Preparation Containing a Chitosan Salt

by Yoshifumi Murata, Youko Kodama, Daijirou Hirai, Kyouko Kofuji and Susumu Kawashima

Molecules 2009, 14(2), 755-762; https://doi.org/10.3390/molecules14020755 - 13 Feb 2009

Cited by 12 | Viewed by 9901

Abstract

The 2-(4-chlorophenoxy)-2-methylpropionic acid (CMP) salt of chitosan (CS), CS-CMP, and that of a CS derivative (CP), were prepared and their ability to adsorb bile acids investigated. CS-CMP and CP-CMP rapidly adsorbed taurocholate (TCA) and glycocholate (GCA) when these bile acids were present together [...] Read more.

The 2-(4-chlorophenoxy)-2-methylpropionic acid (CMP) salt of chitosan (CS), CS-CMP, and that of a CS derivative (CP), were prepared and their ability to adsorb bile acids investigated. CS-CMP and CP-CMP rapidly adsorbed taurocholate (TCA) and glycocholate (GCA) when these bile acids were present together in the medium, with simultaneous release of CMP. A secondary bile acid, taurodeoxycholate, was preferentially adsorbed over TCA and GCA. Alginate gel beads containing CS-CMP did not differ from CS-CMP alone in their manner of bile acids take up. Furthermore, oral administration of CS-CMP to rats resulted in decreased serum cholesterol and triacylglycerol levels for two weeks. Therefore, CS-CMP, as well as a vehiclecontaining CS-CMP, might be a useful agent with which to treat hyperlipidemia Full article

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Open AccessArticle

Ethanolic Extract of Propolis (EEP) Enhances the Apoptosis- Inducing Potential of TRAIL in Cancer Cells

by Ewelina Szliszka, Zenon P. Czuba, Maciej Domino, Bogdan Mazur, Grzegorz Zydowicz and Wojciech Krol

Molecules 2009, 14(2), 738-754; https://doi.org/10.3390/molecules14020738 - 13 Feb 2009

Cited by 236 | Viewed by 27207

Abstract

Ethanolic extract of propolis (EEP) is one of the richest sources of phenolic acids and flavonoids. EEP and its phenolic compounds have been known for various biological activities including immunopotentiation, chemopreventive and antitumor effects. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is [...] Read more.

Ethanolic extract of propolis (EEP) is one of the richest sources of phenolic acids and flavonoids. EEP and its phenolic compounds have been known for various biological activities including immunopotentiation, chemopreventive and antitumor effects. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic toward normal cells. We examined the cytotoxic and apoptotic effect of EEP and phenolic compounds identified in propolis in combination with TRAIL on HeLa cancer cells. HeLa cells were resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL induced death in cancer cells. The percentage of the apoptotic cell after exposure to 50 μg/mL EEP and 100 ng/mL TRAIL increased to 71.10±1.16%. The strongest cytotoxic effect in combination with TRAIL on HeLa cells exhibited apigenin and CAPE at the concentration of 50 μM (58.87±0.75% and 49.59±0.39%, respectively). In this report, we show for the first time that EEP markedly augmented TRAIL mediated apoptosis in cancer cells and confirmed the importance of propolis in chemoprevention of malignant tumors. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics)

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Open AccessArticle

Total Syntheses of (±)-Gusanlung A, (±)-Gusanlung D and 8-Oxyberberrubine and the Uncertainty Concerning the Structures of (-)-Gusanlung A, (-)-Gusanlung D and 8-Oxyberberrubine

by Surachai Nimgirawath, Phansuang Udomputtimekakul, Thitima Apornpisarn, Asawin Wanbanjob and Thongchai Taechowisan

Molecules 2009, 14(2), 726-737; https://doi.org/10.3390/molecules14020726 - 12 Feb 2009

Cited by 3 | Viewed by 9289

Abstract

(±)-Gusanlung A, 8-oxyberberrubine and (±)-gusanlung D have been synthesized by radical cyclisation of the corresponding 2-aroyl-1-methylenetetra- hydroisoquinolines. The ¹H and ¹³C spectra of (-)-gusanlung D were found to be different from those of synthetic (±)-gusanlung D. Careful analyses of the ¹³ [...] Read more.

(±)-Gusanlung A, 8-oxyberberrubine and (±)-gusanlung D have been synthesized by radical cyclisation of the corresponding 2-aroyl-1-methylenetetra- hydroisoquinolines. The ¹H and ¹³C spectra of (-)-gusanlung D were found to be different from those of synthetic (±)-gusanlung D. Careful analyses of the ¹³C spectra of (–)-gusanlung A and natural 8-oxyberberrubine also cast doubt on the correctness of the structures previously assigned to these two compounds. (±)-Gusanlung A and (±)-gusanlung D were inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028. Full article

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Open AccessReview

Factors Affecting Polyphenol Biosynthesis in Wild and Field Grown St. John’s Wort (Hypericum perforatum L. Hypericaceae/Guttiferae)

by Renato Bruni and Gianni Sacchetti

Molecules 2009, 14(2), 682-725; https://doi.org/10.3390/molecules14020682 - 11 Feb 2009

Cited by 123 | Viewed by 23827

Abstract

The increasing diffusion of herbal products is posing new questions: why are products so often different in their composition and efficacy? Which approach is more suitable to increase the biochemical productivity of medicinal plants with large-scale, low-cost solutions? Can the phytochemical profile of [...] Read more.

The increasing diffusion of herbal products is posing new questions: why are products so often different in their composition and efficacy? Which approach is more suitable to increase the biochemical productivity of medicinal plants with large-scale, low-cost solutions? Can the phytochemical profile of a medicinal plant be modulated in order to increase the accumulation of its most valuable constituents? Will polyphenol-rich medicinal crops ever be traded as commodities? Providing a proactive answer to such questions is an extremely hard task, due to the large number of variables involved: intraspecific chemodiversity, plant breeding, ontogenetic stage, post-harvest handling, biotic and abiotic factors, to name but a few. An ideal path in this direction should include the definition of optimum pre-harvesting and post-harvesting conditions and the availability of specific Good Agricultural Practices centered on secondary metabolism enhancement. The first steps to be taken are undoubtedly the evaluation and the organization of scattered data regarding the diverse factors involved in the optimization of medicinal plant cultivation, in order to provide an interdisciplinary overview of main possibilities, weaknesses and drawbacks. This review is intended to be a synopsis of the knowledge on this regard focused on Hypericum perforatum L. (Hypericaceae/Guttiferae) secondary metabolites of phenolic origin, with the aim to provide a reference and suggest an evolution towards the maximization of St. John's Wort bioactive constituents. Factors considered emerged not only from in-field agronomic results, but also from physiological, genetical, biotic, abiotic and phytochemical data that could be scaled up to the application level. To increase quality for final beneficiaries, growers’ profits and ultimately transform phenolic-rich medicinal crops into commodities, the emerging trend suggests an integrated and synergic approach. Agronomy and genetics will need to develop their breeding strategies taking account of the suggestions of phytochemistry, biochemistry, pharmacognosy and pharmacology, without losing sight of the economic balance of the production. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics)

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Open AccessArticle

Anti-inflammatory Activity and PGE2 Inhibitory Properties of Novel Phenylcarbamoylmethyl Ester-Containing Compounds

by Flora Barsoum, Hanan Georgey and Nagwa Abdel-Gawad

Molecules 2009, 14(2), 667-681; https://doi.org/10.3390/molecules14020667 - 11 Feb 2009

Cited by 14 | Viewed by 9253

Abstract

A variety of 4-(un)substituted phenylcarbamoyl methyl ester-containing compounds 3a-d, 5a-d and 7a-d were synthesized via reaction in N,N-dimethylformamide of (un)substituted chloroacetanilides 2a-d with the potassium salts of ibuprofen (1), naproxen (4) and N-acetylanthranilic acid (6). Moreover, other 4-(un)substituted phenylcarbamoylmethyl [...] Read more.

A variety of 4-(un)substituted phenylcarbamoyl methyl ester-containing compounds 3a-d, 5a-d and 7a-d were synthesized via reaction in N,N-dimethylformamide of (un)substituted chloroacetanilides 2a-d with the potassium salts of ibuprofen (1), naproxen (4) and N-acetylanthranilic acid (6). Moreover, other 4-(un)substituted phenylcarbamoylmethyl ester-containing compounds 10a-d were synthesized via the attack of (un)substituted chloroacetanilides 2a-d on one of the carboxylic acid groups of the potassium salt of 4-(2-carboxyethylcarboxamido)benzoic acid (8)in N,N-dimethylformamide, with subsequent cyclization of the other one giving finally a pyrrolidinone structure. Anti-inflammatory properties of the synthesized compounds were evaluated in vivo utilizing a standard acute carrageenan-induced paw oedema method in rats and the most promising prepared anti-inflammatory active agents were evaluated for ulcerogenic liability in rats using ibuprofen and naproxen as reference standards in both screenings. PGE₂ inhibitory properties of the highly promising anti-inflammatory agents synthesized and low gastric ulcerogenic liabilities were tested with a PGE₂assay kit technique. Full article

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Open AccessArticle

Synthesis and Characterization of N-(Arylcarbamothioyl)-cyclohexanecarboxamide Derivatives: The Crystal Structure of N-(Naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide

by Cemal Koray Özer, Hakan Arslan, Don VanDerveer and Nevzat Külcü

Molecules 2009, 14(2), 655-666; https://doi.org/10.3390/molecules14020655 - 10 Feb 2009

Cited by 42 | Viewed by 14014

Abstract

A number of N-(arylcarbamothioyl)cyclohexanecarboxamide derivatives (aryl substituents: phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, o-tolyl, p-tolyl, 3-methoxyphenyl, 4-methoxyphenyl and naphthalen-1yl) have been synthesized. The compounds obtained were characterized by elemental analyses, IR spectroscopy and ¹H-NMR spectroscopy. N-(naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide, H₂L⁹ [...] Read more.

A number of N-(arylcarbamothioyl)cyclohexanecarboxamide derivatives (aryl substituents: phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, o-tolyl, p-tolyl, 3-methoxyphenyl, 4-methoxyphenyl and naphthalen-1yl) have been synthesized. The compounds obtained were characterized by elemental analyses, IR spectroscopy and ¹H-NMR spectroscopy. N-(naphthalen-1-ylcarbamothioyl)cyclohexanecarboxamide, H₂L⁹, was also characterized by a single crystal X-ray diffraction study. This compound, C₁₈H₂₀N₂OS, crystallizes in the triclinic space group Pī, with Z = 2, and unit cell parameters a = 6.9921(14) Å, b = 11.002(2) Å, c = 12.381(3) Å, α = 113.28(3)°, b = 99.38(3)°, and g = 101.85(3)°. The cyclohexane ring adopts a chair conformation. The molecular conformation of the compound is stabilized by an intramolecular (N2-H2•••O1) hydrogen bond which forms a pseudo-six-membered ring. Full article

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Open AccessReview

Prodrugs of Thyrotropin-Releasing Hormone and Related Peptides as Central Nervous System Agents

by Katalin Prokai-Tatrai and Laszlo Prokai

Molecules 2009, 14(2), 633-654; https://doi.org/10.3390/molecules14020633 - 6 Feb 2009

Cited by 18 | Viewed by 13009

Abstract

Prodrug design for brain delivery of small- and medium-sized neuropeptides was reviewed, focusing on thyrotropin-releasing hormone and structurally related peptides as examples. We have summarized our most important advances in methodology, as well as assessed the benefits and limitations of bioreversible chemical manipulation [...] Read more.

Prodrug design for brain delivery of small- and medium-sized neuropeptides was reviewed, focusing on thyrotropin-releasing hormone and structurally related peptides as examples. We have summarized our most important advances in methodology, as well as assessed the benefits and limitations of bioreversible chemical manipulation techniques to achieve targeting of the parent molecules into the central nervous system. The value of prodrug-amenable analogues as potential drug-like central nervous systems agents was highlighted. Full article

(This article belongs to the Special Issue Prodrugs)

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316 KiB

Open AccessCommunication

Polymerization of Cyclic Esters Initiated by Carnitine and Tin (II) Octoate

by Marcin Sobczak and Waclaw Kolodziejski

Molecules 2009, 14(2), 621-632; https://doi.org/10.3390/molecules14020621 - 4 Feb 2009

Cited by 34 | Viewed by 9384

Abstract

Low-molecular weight poly(ε-caprolactone), polylactides and copolymers of ε-caprolactone and lactides were obtained by the polymerization of cyclic esters in the presence of a carnitine/SnOct₂ system. Their structures were proven by means of MALDI-TOF, IR and NMR studies. Effects of temperature, reaction time [...] Read more.

Low-molecular weight poly(ε-caprolactone), polylactides and copolymers of ε-caprolactone and lactides were obtained by the polymerization of cyclic esters in the presence of a carnitine/SnOct₂ system. Their structures were proven by means of MALDI-TOF, IR and NMR studies. Effects of temperature, reaction time and carnitine dosage on the polymerization process were examined. Full article

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309 KiB

Open AccessArticle

Synthesis, Crystal Structure and QuantumChemical Study on 3-Phenylamino-4-Phenyl-1,2,4-Triazole-5-Thione

by Hong-Yan Wang, Pu-Su Zhao, Rong-Qing Li and Su-Min Zhou

Molecules 2009, 14(2), 608-620; https://doi.org/10.3390/molecules14020608 - 4 Feb 2009

Cited by 20 | Viewed by 15115

Abstract

3-Phenylamino-4-phenyl-1,2,4-triazole-5-thione was synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction. Density functional theory calculations of the structure, natural bond orbitals, atomic charge distributions and thermodynamic functions of the title compound were performed at B3LYP/ 6-311G** and PBE1PBE/6-311G**levels of theory, [...] Read more.

3-Phenylamino-4-phenyl-1,2,4-triazole-5-thione was synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction. Density functional theory calculations of the structure, natural bond orbitals, atomic charge distributions and thermodynamic functions of the title compound were performed at B3LYP/ 6-311G** and PBE1PBE/6-311G**levels of theory, respectively. NPA atomic charge distributions indicate that the title compound can be used as a potential multi-dentate ligand to coordinate with various metallic ions. Calculation of the second order optical nonlinearity was also carried out. The thermodynamic properties of C⁰_p,m, S⁰_m and H⁰_m were calculated and correlative equations between the thermodynamic properties and temperatures were also obtained Full article

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90 KiB

Open AccessCommunication

Stereochemistry of 16a-Hydroxyfriedelin and 3-Oxo-16-methylfriedel-16-ene Established by 2D NMR Spectroscopy

by Lucienir Pains Duarte, Roqueline Rodrigues Silva de Miranda, Salomão Bento Vasconcelos Rodrigues Rodrigues, Grácia Divina De Fátima Silva, Sidney Augusto Vieira Filho and Vagner Fernandes Knupp

Molecules 2009, 14(2), 598-607; https://doi.org/10.3390/molecules14020598 - 4 Feb 2009

Cited by 11 | Viewed by 14247

Abstract

Friedelin (1), 3b-friedelinol (2), 28-hydroxyfriedelin (3), 16a-hydroxyfriedelin (4), 30-hydroxyfriedelin (5) and 16a,28-dihydroxyfriedelin (6) were isolated through fractionation of the hexane extract obtained from branches of Salacia elliptica. After a week in CDCl₃ solution, 16a-hydroxyfriedelin (4) reacted turning into 3-oxo-16-methylfriedel-16-ene (7). This is [...] Read more.

Friedelin (1), 3b-friedelinol (2), 28-hydroxyfriedelin (3), 16a-hydroxyfriedelin (4), 30-hydroxyfriedelin (5) and 16a,28-dihydroxyfriedelin (6) were isolated through fractionation of the hexane extract obtained from branches of Salacia elliptica. After a week in CDCl₃ solution, 16a-hydroxyfriedelin (4) reacted turning into 3-oxo-16-methylfriedel-16-ene (7). This is the first report of a dehydration followed by a Nametkin rearrangement of a pentacyclic triterpene in CDCl₃ solution occurring in the NMR tube. These seven pentacyclic triterpenes was identified through NMR spectroscopy and the stereochemistry of compound 4 and 7 was established by 2D NMR (NOESY) spectroscopy and mass spectrometry (GC-MS). It is also the first time that all the ¹³C-NMR and 2D NMR spectral data are reported for compounds 4 and 7. Full article

(This article belongs to the Special Issue Triterpenes and Triterpenoids 2013)

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87 KiB

Open AccessArticle

Antimicrobial Activity of Five Herbal Extracts Against Multi Drug Resistant (MDR) Strains of Bacteria and Fungus of Clinical Origin

by Rosina Khan, Barira Islam, Mohd Akram, Shazi Shakil, Anis Ahmad Ahmad, S. Manazir Ali, Mashiatullah Siddiqui and Asad U. Khan

Molecules 2009, 14(2), 586-597; https://doi.org/10.3390/molecules14020586 - 4 Feb 2009

Cited by 288 | Viewed by 37587

Abstract

Antimicrobial activities of the crude ethanolic extracts of five plants were screened against multidrug resistant (MDR) strains of Escherichia coli, Klebsiella pneumoniae and Candida albicans. ATCCstrains of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus bovis, Pseudimonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae [...] Read more.

Antimicrobial activities of the crude ethanolic extracts of five plants were screened against multidrug resistant (MDR) strains of Escherichia coli, Klebsiella pneumoniae and Candida albicans. ATCCstrains of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus bovis, Pseudimonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae and Candida albicans were also tested. The strains that showed resistance against the maximum number of antibiotics tested were selected for an antibacterial assay. The MDR strains were sensitive to the antimicrobial activity of Acacia nilotica, Syzygium aromaticum and Cinnamum zeylanicum, whereas they exhibited strong resistance to the extracts of Terminalia arjuna and Eucalyptus globulus. Community-acquired infections showed higher sensitivity than the nosocomial infections against these extracts. The most potent antimicrobial plant was A. nilotica (MIC range 9.75-313µg/ml), whereas other crude plant extracts studied in this report were found to exhibit higher MIC values than A. nilotica against community acquired as well as nosocomial infection. This study concludes that A. nilotica, C. zeylanicum and S. aromaticum can be used against multidrug resistant microbes causing nosocomial and community acquired infections. Full article

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Molecules, Volume 14, Issue 2 (February 2009) – 25 articles , Pages 586-903

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