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Molecules, Volume 15, Issue 6 (June 2010), Pages 3775-4489

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Editorial

Jump to: Research, Review

Open AccessEditorial Continued Growth of the Impact Factors of MDPI Open Access Journals
Molecules 2010, 15(6), 4450-4451; doi:10.3390/molecules15064450
Received: 18 June 2010 / Published: 21 June 2010
Cited by 4 | PDF Full-text (62 KB) | HTML Full-text | XML Full-text
Abstract
We are pleased to report the continued increase of the Impact Factors of MDPI journals in 2009 (see Table 1 and Figure 1). As noted in a similar Editorial published in June 2009, the Impact Factors of MDPI journals have been steadily [...] Read more.
We are pleased to report the continued increase of the Impact Factors of MDPI journals in 2009 (see Table 1 and Figure 1). As noted in a similar Editorial published in June 2009, the Impact Factors of MDPI journals have been steadily recovering since the inception of the full Open Access publishing policy in early 2007 [1]. We are pleased to see that all journals now have an Impact Factor much higher than 1. In 2011 the Journal Citation Report (JCR) will include the first official Impact Factor of Entropy , and in 2012, the International Journal of Environmental Research and Public Health will be included for the first time. Nevertheless, we are already able to compute a preliminary impact factor of approximately 1.4 for Entropy [2]. [...] Full article

Research

Jump to: Editorial, Review

Open AccessArticle Photochemical Synthesis of Nucleoside Analogues from Cyclobutanones: Bicyclic and Isonucleosides
Molecules 2010, 15(6), 3816-3828; doi:10.3390/molecules15063816
Received: 8 April 2010 / Revised: 19 May 2010 / Accepted: 24 May 2010 / Published: 26 May 2010
Cited by 3 | PDF Full-text (252 KB)
Abstract
The preparation of two nucleoside analogues are reported. Both syntheses involve a key photochemical ring-expansion of cyclobutanones to an oxacarbene and its subsequent scavenging by 6-chloropurine. The synthesis of a bicyclic (locked) purine starts from a oxabicycloheptanone with a hydroxymethyl pendant. The [...] Read more.
The preparation of two nucleoside analogues are reported. Both syntheses involve a key photochemical ring-expansion of cyclobutanones to an oxacarbene and its subsequent scavenging by 6-chloropurine. The synthesis of a bicyclic (locked) purine starts from a oxabicycloheptanone with a hydroxymethyl pendant. The preparation of an isonucleoside uses a cyclobutanone with an α-substituted 6-chloropurine. Irradiation of the latter produces an isonucleoside and acyclic nucleoside analogues. Full article
(This article belongs to the Special Issue Photochemistry in Organic Synthesis)
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Open AccessArticle A New Cembrane Diterpene from the Bornean Soft Coral Nephthea sp.
Molecules 2010, 15(6), 3857-3862; doi:10.3390/molecules15063857
Received: 20 April 2010 / Revised: 20 May 2010 / Accepted: 13 May 2010 / Published: 26 May 2010
Cited by 8 | PDF Full-text (135 KB)
Abstract
A new cembrane diterpene, 6-acetoxy-7,8-epoxynephthenol acetate (1) was isolated along with a known compound, epoxynephthenol acetate (2), from the organic extract of a Bornean soft coral Nephthea sp. Their structures were elucidated on the basis of spectroscopic analyses [...] Read more.
A new cembrane diterpene, 6-acetoxy-7,8-epoxynephthenol acetate (1) was isolated along with a known compound, epoxynephthenol acetate (2), from the organic extract of a Bornean soft coral Nephthea sp. Their structures were elucidated on the basis of spectroscopic analyses and comparison with those previous literature data. Full article
Open AccessArticle Acid-Catalysed Conversion of Saccharides into Furanic Aldehydes in the Presence of Three-Dimensional Mesoporous Al-TUD-1
Molecules 2010, 15(6), 3863-3877; doi:10.3390/molecules15063863
Received: 13 April 2010 / Revised: 24 May 2010 / Accepted: 26 May 2010 / Published: 28 May 2010
Cited by 39 | PDF Full-text (426 KB)
Abstract
The one-pot acid-catalysed conversion of mono/di/polysaccharides (inulin, xylan, cellobiose, sucrose, glucose, fructose, xylose) into 2-furfuraldehyde (FUR) or 5-hydroxymethylfurfural (HMF) in the presence of aluminium-containing mesoporous TUD-1 (denoted as Al-TUD-1, Si/Al = 21), at 170 ºC was investigated. Xylose gave 60% FUR yield [...] Read more.
The one-pot acid-catalysed conversion of mono/di/polysaccharides (inulin, xylan, cellobiose, sucrose, glucose, fructose, xylose) into 2-furfuraldehyde (FUR) or 5-hydroxymethylfurfural (HMF) in the presence of aluminium-containing mesoporous TUD-1 (denoted as Al-TUD-1, Si/Al = 21), at 170 ºC was investigated. Xylose gave 60% FUR yield after 6 h reaction; hexose-based mono/disaccharides gave less than 20% HMF yield; polysaccharides gave less than 20 wt % FUR or HMF yields after 6 h. For four consecutive 6 h batches of the xylose reaction in the presence of Al-TUD-1, the FUR yields achieved were similar, without significant changes in Si/Al ratio. Full article
(This article belongs to the Special Issue Nano-catalysts and Nano-technologies for Green Organic Synthesis)
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Open AccessCommunication Anti-Proliferative Effect of Camellianin A in Adinandra nitida Leaves and Its Apoptotic Induction in Human Hep G2 and MCF-7 Cells
Molecules 2010, 15(6), 3878-3886; doi:10.3390/molecules15063878
Received: 1 April 2010 / Revised: 14 May 2010 / Accepted: 24 May 2010 / Published: 28 May 2010
Cited by 5 | PDF Full-text (304 KB)
Abstract
Leaves of Adinandra nitida constitute a kind of flavonoid-rich plant food. In this study, camellianin A, the main flavonoid in the leaves of Adinandra nitida,was prepared and identified by high performance liquid chromatography-photodiode array detector-electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). In the [...] Read more.
Leaves of Adinandra nitida constitute a kind of flavonoid-rich plant food. In this study, camellianin A, the main flavonoid in the leaves of Adinandra nitida,was prepared and identified by high performance liquid chromatography-photodiode array detector-electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). In the anticancer assay, it was found camellianin A could inhibit the proliferation of the human hepatocellular liver carcinoma Hep G2 and human breast adenocarcinoma MCF-7 cell lines in a dose-dependent manner and induce the significant increase of the G0/G1 cell population. After treated by camellianin A, phosphatidylserine of Hep G2 and MCF-7 cells could translocate significantly to the surface of the membrane. The increase of an early apoptotic population of Hep G2 and MCF-7 cells was observed. It was concluded that camellianin A not only affected the progress of the cell cycle, but also induced cells to enter into apoptosis. Full article
Open AccessArticle Synthesis and Adrenolytic Activity of New Propanolamines
Molecules 2010, 15(6), 3887-3904; doi:10.3390/molecules15063887
Received: 20 April 2010 / Revised: 23 May 2010 / Accepted: 26 May 2010 / Published: 28 May 2010
PDF Full-text (286 KB)
Abstract The synthesis of (2R,S)-1-(6-methoxy-4-(methoxymethyl)-1H-indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2R,S)-1-(4-methoxy-6-(methoxymethyl)-1H-indol-5-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol is described. The compounds were tested for electrographic, antiarrhythmic, hypotensive, and spasmolytic activity, as well as for a1-, a2- and β1-adrenoceptor binding affinity. Full article
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Open AccessArticle Bovine and Human Serum Albumin Interactions with 3-Carboxyphenoxathiin Studied by Fluorescence and Circular Dichroism Spectroscopy
Molecules 2010, 15(6), 3905-3919; doi:10.3390/molecules15063905
Received: 5 May 2010 / Accepted: 26 May 2010 / Published: 1 June 2010
Cited by 61 | PDF Full-text (370 KB)
Abstract
The interactions of 3-carboxyphenoxathiin with Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) have been studied by fluorescence and circular dichroism spectroscopy. The binding of 3-carboxyphenoxathiin quenches the BSA and HSA fluorescence, revealing a 1:1 interaction with a binding constant of [...] Read more.
The interactions of 3-carboxyphenoxathiin with Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) have been studied by fluorescence and circular dichroism spectroscopy. The binding of 3-carboxyphenoxathiin quenches the BSA and HSA fluorescence, revealing a 1:1 interaction with a binding constant of about 105 M-1. In addition, according to the synchronous fluorescence spectra of BSA and HSA in presence of 3-carboxyphenoxathiin, the tryptophan residues of the proteins are most perturbed by the binding process. Finally, the distance between the acceptor, 3-carboxyphenoxathiin, and the donor, BSA or HSA, was estimated on the basis of the Förster resonance energy transfer (FRET). The fluorescence results are correlated with those obtained from the circular dichroism spectra, which reveal the change of the albumin conformation during the interaction process. Full article
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Open AccessArticle Antifungal Activity and Nail Permeation of Nail Lacquer Containing Piper regnellii (Miq.) C. CD. var. pallescens (C. DC.) Yunck (Piperaceae) Leave Extracts and Derivatives
Molecules 2010, 15(6), 3920-3931; doi:10.3390/molecules15063920
Received: 31 March 2010 / Revised: 11 May 2010 / Accepted: 12 May 2010 / Published: 1 June 2010
Cited by 3 | PDF Full-text (3229 KB)
Abstract
The dermatophytes are filamentous fungi that cause cutaneous fungal infections because they use keratin as a nutrient source. For this study the antidermatophyte activity of the extracts and derivates from leaves of Piper regnellii was analyzed. From the dichloromethane extract (EBD) neolignans [...] Read more.
The dermatophytes are filamentous fungi that cause cutaneous fungal infections because they use keratin as a nutrient source. For this study the antidermatophyte activity of the extracts and derivates from leaves of Piper regnellii was analyzed. From the dichloromethane extract (EBD) neolignans such as eupomatenoid-3 and eupomatenoid-5 were obtained, and it was submitted to fractionation to remove the green residue, designated as the chloroform fraction (FF). Extracts, chloroform fraction and compounds were tested against Trichophyton rubrum ATCC 28189 to determine the minimum inhibitory concentration (MIC). The chloroform fraction was incorporated to nail lacquer that was analyzed by photoacoustic spectroscopy, in vitro assay and scanning electronic microscopy. For antifungal activity in solid medium the dichloromethane extract and chloroform fraction were used. The compounds eupomatenoid-3 and eupomatenoid-5 were less active than the dichloromethane extract against T. rubrum. EBD and FF showed moderate activity in hyphal growth inhibition in solid medium and EBD did not link to ergosterol. Nail lacquer containing the chloroform fraction showed good penetration through the nail as determined by photoacoustic spectroscopy. From in vitro studies it was observed that nail lacquer concentrations above 20 mg/mL prevented the growth of fungi, but concentrations up to 2.5 inhibited the growth. Scanning electronic microscopy was used to confirm the in vitro nail lacquer activity results. The specie P. regnellii showed great antifungal activity against T. rubrum, and nail lacquer containing its chloroform fraction has great potential to treat onychomycosis caused by these microorganisms. Full article
Open AccessArticle Synthesis, Characterization and Biological Studies of Some Novel Thieno[2,3-d]pyrimidines
Molecules 2010, 15(6), 3932-3957; doi:10.3390/molecules15063932
Received: 29 March 2010 / Revised: 20 May 2010 / Accepted: 27 May 2010 / Published: 1 June 2010
Cited by 13 | PDF Full-text (348 KB)
Abstract
Several 2-unsubstituted thieno[2,3-d]pyrimidines have been prepared from 2-aminothiophene-3-carboxylic acid esters and their carbonitrile analogs. Some triazolo-thienopyrimidine and 2-thioxothienopyrimidine representatives have also been synthesized using thermal and microwave (MW) irradiation techniques. Structures of the prepared compounds were elucidated on the basis of IR, [...] Read more.
Several 2-unsubstituted thieno[2,3-d]pyrimidines have been prepared from 2-aminothiophene-3-carboxylic acid esters and their carbonitrile analogs. Some triazolo-thienopyrimidine and 2-thioxothienopyrimidine representatives have also been synthesized using thermal and microwave (MW) irradiation techniques. Structures of the prepared compounds were elucidated on the basis of IR, NMR, 2D NMR and mass spectral data. The biological activity of some selected synthesized compounds was also examined. Full article
Open AccessArticle Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
Molecules 2010, 15(6), 3958-3992; doi:10.3390/molecules15063958
Received: 8 March 2010 / Revised: 13 May 2010 / Accepted: 15 May 2010 / Published: 1 June 2010
Cited by 9 | PDF Full-text (3759 KB)
Abstract
Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone [...] Read more.
Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
Open AccessArticle A New Azaphilone, Kasanosin C, from an Endophytic Talaromyces sp. T1BF
Molecules 2010, 15(6), 3993-3997; doi:10.3390/molecules15063993
Received: 20 April 2010 / Revised: 17 May 2010 / Accepted: 24 May 2010 / Published: 1 June 2010
Cited by 9 | PDF Full-text (217 KB)
Abstract
The strain T1BF was isolated from the old bast tissue of Taxus yunnanensis and determined to be a member of Talaromyces. The extracts from the solid fermentation of Talaromycessp. T1BF were purified and obtained three azaphilones, including a new one. [...] Read more.
The strain T1BF was isolated from the old bast tissue of Taxus yunnanensis and determined to be a member of Talaromyces. The extracts from the solid fermentation of Talaromycessp. T1BF were purified and obtained three azaphilones, including a new one. They were identified on the basis of spectral data as 6α-hydroxy-7β-methyl-8-oxo-3-((E)- prop-1-en-1-yl)-5,6,7,8-tetrahydro-1H-isochromen-7-yl-4'-hydroxy-2'-methoxy-6'-methyl- benzoate, named as kasanosin C (1), entonaemin A (2) and (+)-mitorubrin (3). Full article
Open AccessArticle Direct Enzymatic Route for the Preparation of Novel Enantiomerically Enriched Hydroxylated β-Amino Ester Stereoisomers
Molecules 2010, 15(6), 3998-4010; doi:10.3390/molecules15063998
Received: 6 May 2010 / Revised: 25 May 2010 / Accepted: 28 May 2010 / Published: 1 June 2010
Cited by 8 | PDF Full-text (585 KB)
Abstract
Enantiomerically enriched hydroxy-substituted b-amino esters have been synthesized through CAL-B-catalyzed enantioselective hydrolysis in organic media. Moderate to good enantiomeric excess values (ee ≥ 52%) were obtained when the CAL-B-catalyzed reactions were performed in t-BuOMe, at 60 ºC with 0.5 [...] Read more.
Enantiomerically enriched hydroxy-substituted b-amino esters have been synthesized through CAL-B-catalyzed enantioselective hydrolysis in organic media. Moderate to good enantiomeric excess values (ee ≥ 52%) were obtained when the CAL-B-catalyzed reactions were performed in t-BuOMe, at 60 ºC with 0.5 equiv. of added H2O as nucleophile. Full article
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Open AccessArticle Aquilarin A, a New Benzenoid Derivative from the Fresh Stem of Aquilaria sinensis
Molecules 2010, 15(6), 4011-4016; doi:10.3390/molecules15064011
Received: 31 March 2010 / Revised: 19 May 2010 / Accepted: 24 May 2010 / Published: 1 June 2010
Cited by 19 | PDF Full-text (135 KB)
Abstract
Chemical investigation of the EtOH extract of the fresh stem of Aquilaria sinensis collected in Hainan Province of China resulted in the isolation of a new benzenoid, named aquilarin A (1), together with two known compounds balanophonin (2) [...] Read more.
Chemical investigation of the EtOH extract of the fresh stem of Aquilaria sinensis collected in Hainan Province of China resulted in the isolation of a new benzenoid, named aquilarin A (1), together with two known compounds balanophonin (2) and (+)-lariciresinol (3). Their structures were elucidated by a study of their physical and spectral data. Compounds 2 and 3 exhibited cytotoxicity against SGC-7901 and SMMC-7721 cell lines. Full article
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Open AccessArticle Quantum Chemical Calculations on the Interaction between Flavonol and Functional Monomers (Methacrylic Acid and 4-Vinylpyridine) in Molecularly Imprinted Polymers
Molecules 2010, 15(6), 4017-4032; doi:10.3390/molecules15064017
Received: 1 May 2010 / Revised: 17 May 2010 / Accepted: 2 June 2010 / Published: 2 June 2010
Cited by 7 | PDF Full-text (599 KB)
Abstract
Quantum chemical calculations were performed to characterize the interaction of the flavonol molecule (FL) with methacrylic acid (MAA) and 4-vinylpyridine (4VPy) in the formation of imprinted polymers. The polarizable continuum model (PCM) was used to gain insight on the type of interaction [...] Read more.
Quantum chemical calculations were performed to characterize the interaction of the flavonol molecule (FL) with methacrylic acid (MAA) and 4-vinylpyridine (4VPy) in the formation of imprinted polymers. The polarizable continuum model (PCM) was used to gain insight on the type of interaction between the reactant molecules under vacuum conditions and in the presence of different solvents. The effect of solvent on the pre-polymerization complex formation was evaluated through the stability energy, in which chloroform behaves as the best solvent for the synthesis of the imprinted polymers since it facilitates the reaction by lowering its degree of stabilization. The reactivity was analyzed in terms of the electrostatic surface potential (ESP) and Mulliken charge. By means of these results, it has been possible to determine two potential recognition sites for the interaction of the MAA monomer and one for the 4VPy in relation to the strength of interaction with FL. In this concern, the interaction of the system FL-MAA is stronger than FL-4VPy. Full article
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Open AccessArticle Synthesis and in vitro Cytotoxicity of Novel Ursolic Acid Derivatives
Molecules 2010, 15(6), 4033-4040; doi:10.3390/molecules15064033
Received: 21 April 2010 / Revised: 13 May 2010 / Accepted: 26 May 2010 / Published: 4 June 2010
Cited by 22 | PDF Full-text (120 KB)
Abstract
In an effort to improve potential hepatoprotective and anti-tumor activities, eight novel ursolic acid (UA) derivatives were designed and synthesized with substitution at positions of C-3, C-11and C-28 of UA. Their structures were confirmed using IR, MS and 1H-NMR and elemental [...] Read more.
In an effort to improve potential hepatoprotective and anti-tumor activities, eight novel ursolic acid (UA) derivatives were designed and synthesized with substitution at positions of C-3, C-11and C-28 of UA. Their structures were confirmed using IR, MS and 1H-NMR and elemental analysis. Their in vitro cytotoxicity against various cancer cell lines (HeLa, SKOV3 and BGC-823) was evaluated by the standard MTT assay. Among them, compound 13 exhibited more potent cytotoxicity than ursolic acid. Full article
Open AccessArticle Receptor-Based Virtual Screening of EGFR Kinase Inhibitors from the NCI Diversity Database
Molecules 2010, 15(6), 4041-4054; doi:10.3390/molecules15064041
Received: 16 March 2010 / Revised: 26 May 2010 / Accepted: 28 May 2010 / Published: 4 June 2010
Cited by 12 | PDF Full-text (5067 KB) | Supplementary Files
Abstract
Epidermal growth factor receptor (EGFR) abnormalities have been associated with several types of human cancer. The crystal structures of its tyrosine kinase domain (EGFR-TK) complexed with small molecule inhibitors revealed the kinase inhibition modes, prompting us to search for novel anti-cancer drugs. [...] Read more.
Epidermal growth factor receptor (EGFR) abnormalities have been associated with several types of human cancer. The crystal structures of its tyrosine kinase domain (EGFR-TK) complexed with small molecule inhibitors revealed the kinase inhibition modes, prompting us to search for novel anti-cancer drugs. A total of 1,990 compounds from the National Cancer Institute (NCI) diversity set with nonredundant structures have been tested to inhibit cancer cell lines with unknown mechanism. Cancer inhibition through EGFR-TK is one of the mechanisms of these compounds. In this work, we performed receptor-based virtual screening against the NCI diversity database. Using two different docking algorithms, AutoDock and Gold, combined with subsequent post-docking analyses, we found eight candidate compounds with high scoring functions that all bind to the ATP-competitive site of the kinase. None of these compounds belongs to the main group of the currently known EGFR-TK inhibitors. Binding mode analyses revealed that the way these compounds complexed with EGFR-TK differs from quinazoline inhibitor binding and the interaction mainly involves hydrophobic interactions. Also, the common kinase-inhibitor (NH---N and CO---HC) hydrogen bonds between the hinge region and the hit compounds are rarely observed. Our results suggest that these molecules could be developed as novel lead compounds in anti-cancer drug design. Full article
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Open AccessArticle Determination of the Volatile Constituents in Radix Flemingiae Philippinensis by GC-MS and a Heuristic Evolving Latent Projection Method
Molecules 2010, 15(6), 4055-4066; doi:10.3390/molecules15064055
Received: 10 March 2010 / Revised: 24 May 2010 / Accepted: 28 May 2010 / Published: 4 June 2010
Cited by 2 | PDF Full-text (253 KB)
Abstract
With the help of chemometric resolution methods, a technique for qualitative and quantitative determination of the volatile chemical constituents in Radix Flemingiae Philippinensis by chromatography-mass spectrometry was developed. After the overlapping chromatographic peaks were resolved into pure chromatograms and spectra using a [...] Read more.
With the help of chemometric resolution methods, a technique for qualitative and quantitative determination of the volatile chemical constituents in Radix Flemingiae Philippinensis by chromatography-mass spectrometry was developed. After the overlapping chromatographic peaks were resolved into pure chromatograms and spectra using a heuristic evolving latent projections (HELP) method, qualitative analysis was performed by similarity search of the obtained pure mass spectrum of each component in the NIST library and the quantitative results were obtained by calculating the total two-way response volume. A total of 63 components were separated and 55 components were identified, accounting for 90.62% of the total content. The main components were farnesol isomer and β-caryophyllene, accounting for 31.33% and 12.60% of the total content, respectively. The obtained results can provide useful information for further study and development of Radix Flemingiae Philippinensis. Full article
Open AccessArticle Pharmaceutical Composition of Valsartan: β-Cyclodextrin: Physico–Chemical Characterization and Anti-Hypertensive Evaluation
Molecules 2010, 15(6), 4067-4084; doi:10.3390/molecules15064067
Received: 17 May 2010 / Accepted: 27 May 2010 / Published: 4 June 2010
Cited by 18 | PDF Full-text (2312 KB)
Abstract
Valsartan, a water-insoluble drug, is mainly used in the treatment of hypertension albeit with reduced oral bioavailability. The aim of work was to develop a valsartan:β-cyclodextrin (VAL:β-CD) pharmaceutical composition in order to improve its water solubility and bioavailability. The VAL:β-CD complexes were [...] Read more.
Valsartan, a water-insoluble drug, is mainly used in the treatment of hypertension albeit with reduced oral bioavailability. The aim of work was to develop a valsartan:β-cyclodextrin (VAL:β-CD) pharmaceutical composition in order to improve its water solubility and bioavailability. The VAL:β-CD complexes were prepared by the kneading, solid dispersion and freeze-drying methods, of which the freeze-drying method (FDY) was found to be the best to prepare an inclusion complex. A physical mixtyure PM was also prepared. Complexes were characterized by thermal analysis, Fourier transformed- infrared (FTIR) spectroscopy, Powder X-ray diffractometry, intrinsic dissolution and NMR (2D-ROESY). Phase-solubility analysis showed AL-type diagrams with β-cyclodextrin (β-CD). Microcalorimetric titrations suggested the formation of 1:1 inclusion complex between VAL and β-CD. The apparent stability constants K1:1 calculated from phase-solubility plots were 165.4 M-1 (298 K), 145.0 M-1 (303 K) and 111.3 M-1 (310 K). In vivo experiments in rats showed that reduction in arterial pressure for the FDY complex is better than with valsartan used alone. The better activity of FDY can be attributed to the higher solubility of valsartan after inclusion in the cyclodextrin cavity, as suggest by the intrinsic dissolution studies. Full article
Open AccessArticle Synthesis and Biological Evaluation of a γ-Cyclodextrin-based Formulation of the Anticancer Agent 5,6,11,12,17,18,23,24- Octahydrocyclododeca[1,2-b:4,5-b’:7,8-b’’:10,11-b’’’]tetraindole (CTet)
Molecules 2010, 15(6), 4085-4093; doi:10.3390/molecules15064085
Received: 21 April 2010 / Revised: 27 May 2010 / Accepted: 1 June 2010 / Published: 4 June 2010
Cited by 10 | PDF Full-text (165 KB)
Abstract
5,6,11,12,17,18,23,24-octahydrocyclododeca[1,2-b:4,5-b’:7,8-b’’:10,11- b’’’]tetrai ndole (CTet), an indole-3-carbinol (I3C) metabolite endowed with anticancer properties, is poorly soluble in the solvents most frequently used in biological tests. This study indicates that the use of γ-cyclodextrin (γ-CD) avoids this problem. Formulated with γ-CD CTet is a [...] Read more.
5,6,11,12,17,18,23,24-octahydrocyclododeca[1,2-b:4,5-b’:7,8-b’’:10,11- b’’’]tetrai ndole (CTet), an indole-3-carbinol (I3C) metabolite endowed with anticancer properties, is poorly soluble in the solvents most frequently used in biological tests. This study indicates that the use of γ-cyclodextrin (γ-CD) avoids this problem. Formulated with γ-CD CTet is a potent inhibitor of DNA synthesis in both estrogen receptor positive (MCF-7) and estrogen receptor negative (MDA-MB-231) human breast cell lines (IC50 = 1.20 ± 0.04 μM and 1.0 ± 0.1 μM, respectively). Full article
Open AccessArticle An Expeditious Synthesis of [1,2]Isoxazolidin-5-ones and [1,2]Oxazin-6-ones from Functional Allyl Bromide Derivatives
Molecules 2010, 15(6), 4094-4101; doi:10.3390/molecules15064094
Received: 26 April 2010 / Revised: 14 May 2010 / Accepted: 24 May 2010 / Published: 7 June 2010
Cited by 1 | PDF Full-text (115 KB) | Retraction
Abstract Reaction of allyl bromide (Z)-1 and (Z)-2 with N-substituted hydroxylamine hydrochlorides in presence of tert-butoxide in tert-butanol at reflux provides a short and effective route to [1,2]isoxazolidin-5-ones 3 and [1,2]oxazin-6-ones 4. Full article
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Open AccessArticle Synthesis of a New Series of N,N’-Dimethyltetrahydrosalen (H2 [H2Me]salen) Ligands by the Reductive Ring-Opening of 3,3'-Ethylene-bis(3,4-dihydro-6-substituted-2H-1,3-benzoxazines)
Molecules 2010, 15(6), 4102-4110; doi:10.3390/molecules15064102
Received: 26 April 2010 / Revised: 7 May 2010 / Accepted: 11 May 2010 / Published: 7 June 2010
Cited by 4 | PDF Full-text (104 KB)
Abstract
A new series of N,N'-bis(2'-hydroxy-5'-substituted-benzyl)-N,N´-dimethylethane-1,2-diamines (N,N'-dimethyltetrahydrosalen) ligands were prepared in good yield by reduction of the respective 3,3'-ethylene-bis(3,4-dihydro-6-substituted-2H-1,3-benzoxazine) precursors with sodium borohydride . The ligands were characterized by IR, NMR, and [...] Read more.
A new series of N,N'-bis(2'-hydroxy-5'-substituted-benzyl)-N,N´-dimethylethane-1,2-diamines (N,N'-dimethyltetrahydrosalen) ligands were prepared in good yield by reduction of the respective 3,3'-ethylene-bis(3,4-dihydro-6-substituted-2H-1,3-benzoxazine) precursors with sodium borohydride . The ligands were characterized by IR, NMR, and elemental analysis, which showed the compounds to be consistent with the proposed structures. Ring-opening reactions of bis-1,3-benzoxazines in the presence of sodium borohydride to produce N,N’-dimethylated tetrahydrosalens (H2 [H2Me]salen) have not been reported in the literature. Full article
Open AccessArticle Rhodium-Catalyzed Linear Codimerization and Cycloaddition of Ketenes with Alkynes
Molecules 2010, 15(6), 4189-4200; doi:10.3390/molecules15064189
Received: 11 May 2010 / Revised: 25 May 2010 / Accepted: 7 June 2010 / Published: 9 June 2010
Cited by 7 | PDF Full-text (286 KB)
Abstract
A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, [...] Read more.
A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, RhCl(PPh3)3, and are highly dependent on the structure and reactivity of the starting ketenes. Full article
(This article belongs to the Special Issue Cycloaddition Reactions in Organic Synthesis)
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Open AccessArticle Synthesis of 2-(9,10-Dihydro-9,10-propanoanthracen-9-yl)-N-methylethanamine via a [4+2] Cycloaddition
Molecules 2010, 15(6), 4201-4206; doi:10.3390/molecules15064201
Received: 19 May 2010 / Revised: 31 May 2010 / Accepted: 1 June 2010 / Published: 9 June 2010
Cited by 3 | PDF Full-text (126 KB)
Abstract The synthesis of the tetracyclic molecule 2-(9,10-dihydro-9,10-propano-anthracen-9-yl)-N-methylethanamine(2)as a homologue of the antidepressant 1-(9,10-dihydro-9,10-ethanoanthracen-9-yl)-N-methylmethaneamine (1) was described. The key intermediate 9-(prop-2-en-1-yl)-9,10-dihydro-9,10-propanoanthracen-12-one (7)was successfully synthesized via a [4+2] cycloaddition of α-bromoacrolein and 9-allyl-anthracene, followed by ring expansion and samarium diiodide deoxygenation. Full article
Open AccessCommunication An Effective Microwave-Induced Iodine-Catalyzed Method for the Synthesis of Quinoxalines via Condensation of 1,2-Diamines with 1,2-Dicarbonyl Compounds
Molecules 2010, 15(6), 4207-4212; doi:10.3390/molecules15064207
Received: 28 March 2010 / Revised: 14 May 2010 / Accepted: 9 June 2010 / Published: 9 June 2010
Cited by 34 | PDF Full-text (383 KB)
Abstract A microwave-induced iodine-catalyzed simple, rapid and convenient synthesis of different types of quinoxalines via condensation of 1,2-diamines with 1,2-dicarbonyl compounds has been accomplished with an excellent yield. Full article
(This article belongs to the Special Issue Organic Iodine Chemistry)
Open AccessArticle Free Radical Scavenging Activity and Anthocyanin Profile of Cabernet Sauvignon Wines from the Balkan Region
Molecules 2010, 15(6), 4213-4226; doi:10.3390/molecules15064213
Received: 20 April 2010 / Revised: 2 June 2010 / Accepted: 7 June 2010 / Published: 10 June 2010
Cited by 14 | PDF Full-text (308 KB)
Abstract
The present study is focused on anthocyanin derivatives characterizing the antioxidant activity of Cabernet Sauvignon wines produced from different vineyard regions in the Balkans. These bioactive compounds were quantified with a high performance liquid chromatography (HPLC)-diode array detection (DAD) method. The antiradical [...] Read more.
The present study is focused on anthocyanin derivatives characterizing the antioxidant activity of Cabernet Sauvignon wines produced from different vineyard regions in the Balkans. These bioactive compounds were quantified with a high performance liquid chromatography (HPLC)-diode array detection (DAD) method. The antiradical activity was estimated by the ability of the wine to scavenge the stable 2,2`-diphenyl-1-picrylhydrazyl free radical (DPPH·). The results show that the total anthocyanin content varied from 205.88 to 1940.28 mg/L, depending on agroclimatic factors and the enological practices of the corresponding vineyard region. The most prominent antocyanin in all investigated Cabernet Sauvignon wines was malvidin-3-O-monoglucoside, which accounted for 50.57% of total content, followed by its acetyl derivatives, 15.45%, and p-coumaryl derivatives 5.66%. The relationship between the anthocyanin derivatives and free radical scavenging activity is discussed. A high correlation between total anthocyanin content and DPPH· scavenging ability of tested wines was confirmed (r2 = 0.9619). The significant correlations were obtained between antiradical activity and the sum of 3-monoglucoside (r2 = 0.95594), the sum of 3-acetyl-3-glucoside (r2 = 0.9728) and the sum of p-coumaryl-3-glucoside (r2 = 0.8873) of wine samples. It can be concluded that, the anthocyanin composition can be used as biochemical marker for the authenticity of red grape cultivar and their corresponding single-cultivar wine. Full article
Open AccessArticle Evaluation of Carbohydrates in Natural and Cultured Cordyceps by Pressurized Liquid Extraction and Gas Chromatography Coupled with Mass Spectrometry
Molecules 2010, 15(6), 4227-4241; doi:10.3390/molecules15064227
Received: 31 May 2010 / Revised: 9 June 2010 / Accepted: 10 June 2010 / Published: 11 June 2010
Cited by 30 | PDF Full-text (1150 KB)
Abstract
Free and polymeric carbohydrates in Cordyceps, a valued edible mushroom and well-known traditional Chinese medicine, were determined using stepwise pressurized liquid extraction (PLE) extraction and GC-MS. Based on the optimized PLE conditions, acid hydrolysis and derivatization, ten monosaccharides, namely rhamnose, ribose, [...] Read more.
Free and polymeric carbohydrates in Cordyceps, a valued edible mushroom and well-known traditional Chinese medicine, were determined using stepwise pressurized liquid extraction (PLE) extraction and GC-MS. Based on the optimized PLE conditions, acid hydrolysis and derivatization, ten monosaccharides, namely rhamnose, ribose, arabinose, xylose, mannose, glucose, galactose, mannitol, fructose and sorbose in 13 samples of natural and cultured Cordyceps were qualitatively and quantitatively analyzed and compared with myo-inositol hexaacetate as internal standard. The results showed that natural C. sinensis contained more than 7.99% free mannitol and a small amount of glucose, while its polysaccharides were usually composed of mannose, glucose and galactose with a molar ratio of 1.00:16.61~3.82:1.60~1.28. However, mannitol in cultured C. sinensis and cultured C. militaris were less than 5.83%, and free glucose was only detected in a few samples, while their polysaccharides were mainly composed of mannose, glucose and galactose with molar ratios of 1.00:3.01~1.09:3.30~1.05 and 1.00:2.86~1.28:1.07~0.78, respectively. Natural and cultured Cordyceps could be discriminated by hierarchical clustering analysis based on its free carbohydrate contents. Full article
(This article belongs to the Special Issue Phytochemicals with Signaling, Medicinal and Therapeutic Properties)
Open AccessArticle Synthesis of Bosutinib from 3-Methoxy-4-hydroxybenzoic Acid
Molecules 2010, 15(6), 4261-4266; doi:10.3390/molecules15064261
Received: 9 April 2010 / Revised: 13 May 2010 / Accepted: 9 June 2010 / Published: 11 June 2010
Cited by 12 | PDF Full-text (94 KB)
Abstract
This paper reports a novel synthesis of bosutinib starting from 3-methoxy-4-hydroxybenzoic acid. The process starts with esterification of the starting material, followed by alkylation, nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1 [...] Read more.
This paper reports a novel synthesis of bosutinib starting from 3-methoxy-4-hydroxybenzoic acid. The process starts with esterification of the starting material, followed by alkylation, nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all the compounds were determined by HPLC. Full article
Open AccessArticle Synthesis and Bioactivity of N-Benzoyl-N'-[5-(2'-substituted phenyl)-2-furoyl] Semicarbazide Derivatives
Molecules 2010, 15(6), 4267-4282; doi:10.3390/molecules15064267
Received: 5 May 2010 / Revised: 31 May 2010 / Accepted: 2 June 2010 / Published: 11 June 2010
Cited by 14 | PDF Full-text (196 KB)
Abstract
In order to find novel chitin synthesis inhibitors (CSIs) with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 15 novel derivatives containing furan moieties were designed by converting the urea linkage of benzoylphenylureas into a [...] Read more.
In order to find novel chitin synthesis inhibitors (CSIs) with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 15 novel derivatives containing furan moieties were designed by converting the urea linkage of benzoylphenylureas into a semicarbazide and changing the aniline part into furoyl groups. The title compounds were synthesized by the reaction of substituted benzoyl isocyanates with 5-(substituted phenyl)-2-furoyl hydrazine, and the structures were confirmed by IR, 1H-NMR, elemental analysis and single crystal X-ray diffraction analyses (compound E2). The bioassay results indicated that the title compounds exhibit good insecticidal activity, especially towards Plutella xylostella L., but had lower fungicidal activity. Inspiringly, the title compounds possessed obvious anticancer activity against human promyelocytic leukemic cell line (HL-60), and some of the title compounds also had activity against human hepatocellular carcinoma cell line (Bel-7402), human gastric carcinoma cell line (BGC-823), and human nasopharyngeal carcinoma cell line (KB). The results indicated that the linkage in the lead compounds was important to the bioactivity and spectra. The modification on the urea linkage is an effective strategy to discover new pesticide and drug candidates. Full article
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Open AccessArticle Bisbenzamidines as Antifungal Agents. Are Both Amidine Functions Required to Observe an Anti-Pneumocystis carinii Activity?
Molecules 2010, 15(6), 4283-4293; doi:10.3390/molecules15064283
Received: 26 May 2010 / Revised: 1 June 2010 / Accepted: 7 June 2010 / Published: 11 June 2010
Cited by 6 | PDF Full-text (126 KB)
Abstract
A library of 19 novel 4-(4-phenylpiperazine-1-yl)benzamidines has been synthesized and evaluated in vitro against Pneumocystis carinii. Among these compounds, N-ethyl- and N-hexyl-4-(4-phenylpiperazine-1-yl)benzamidines emerged as the most promising compounds, with inhibition percentages at 10.0 µg/mL of 87% and 96%, respectively. [...] Read more.
A library of 19 novel 4-(4-phenylpiperazine-1-yl)benzamidines has been synthesized and evaluated in vitro against Pneumocystis carinii. Among these compounds, N-ethyl- and N-hexyl-4-(4-phenylpiperazine-1-yl)benzamidines emerged as the most promising compounds, with inhibition percentages at 10.0 µg/mL of 87% and 96%, respectively. Those compounds remained active at 0.1 µg/mL. Full article
(This article belongs to the Special Issue ECSOC-13)
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Open AccessArticle Design of Novel 4-Hydroxy-chromene-2-one Derivatives as Antimicrobial Agents
Molecules 2010, 15(6), 4294-4308; doi:10.3390/molecules15064294
Received: 23 April 2010 / Revised: 31 May 2010 / Accepted: 7 June 2010 / Published: 11 June 2010
Cited by 16 | PDF Full-text (544 KB)
Abstract
This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs), against twenty four microorganism cultures, Gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130–500 μg/mL) and 9c [...] Read more.
This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs), against twenty four microorganism cultures, Gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130–500 μg/mL) and 9c (31.25–62.5 μg/mL), presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 μg/mL) against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity. Full article
Open AccessArticle Phytotoxic Activities of Mediterranean Essential Oils
Molecules 2010, 15(6), 4309-4323; doi:10.3390/molecules15064309
Received: 28 April 2010 / Revised: 9 June 2010 / Accepted: 11 June 2010 / Published: 14 June 2010
Cited by 38 | PDF Full-text (275 KB)
Abstract
Twelve essential oils from Mediterranean aromatic plants were tested for their phytotoxic activity, at different doses, against the germination and the initial radicle growth of seeds of Raphanus sativus, Lactuca sativa and Lepidium sativum. The essential oils were obtained from [...] Read more.
Twelve essential oils from Mediterranean aromatic plants were tested for their phytotoxic activity, at different doses, against the germination and the initial radicle growth of seeds of Raphanus sativus, Lactuca sativa and Lepidium sativum. The essential oils were obtained from Hyssopus officinalis, Lavandula angustifolia, Majorana hortensis, Melissa officinalis, Ocimum basilicum, Origanum vulgare, Salvia officinalis and Thymus vulgaris (Lamiaceae), Verbena officinalis (Verbenaceae), Pimpinella anisum, Foeniculum vulgare and Carum carvi (Apiaceae). The germination and radicle growth of tested seeds were affected in different ways by the oils. Thyme, balm, vervain and caraway essential oils were more active against both germination and radicle elongation. Full article
Open AccessArticle Antioxidant Activities, Total Phenolics and Flavonoids Content in Two Varieties of Malaysia Young Ginger (Zingiber officinale Roscoe)
Molecules 2010, 15(6), 4324-4333; doi:10.3390/molecules15064324
Received: 18 April 2010 / Revised: 20 May 2010 / Accepted: 24 May 2010 / Published: 14 June 2010
Cited by 105 | PDF Full-text (134 KB)
Abstract
Ginger (Zingiber officinale Roscoe) is a well known and widely used herb, especially in Asia, which contains several interesting bioactive constituents and possesses health promoting properties. In this study, the antioxidant activities of methanol extracts from the leaves, stems and rhizomes [...] Read more.
Ginger (Zingiber officinale Roscoe) is a well known and widely used herb, especially in Asia, which contains several interesting bioactive constituents and possesses health promoting properties. In this study, the antioxidant activities of methanol extracts from the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia Bara) were assessed in an effort to compare and validate the medicinal potential of the subterranean part of the young ginger. The antioxidant activity and phenolic contents of the leaves as determined by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay and the total amounts of phenolics and flavonoids were higher than those of the rhizomes and stems. On the other hand, the ferric reducing/antioxidant potential (FRAP) activity of the rhizomes was higher than that of the leaves. At low concentration the values of the leaves’ inhibition activity in both varieties were significantly higher than or comparable to those of the young rhizomes. Halia Bara had higher antioxidant activities as well as total contents of phenolic and flavonoid in comparison with Halia Bentong. This study validated the medicinal potential of the leaves and young rhizome of Zingiber officinale (Halia Bara) and the positive relationship between total phenolics content and antioxidant activities in Zingiber officinale. Full article
Open AccessArticle β-Enamino Esters in Heterocyclic Synthesis: Synthesis of Pyrazolone and Pyridinone Derivatives
Molecules 2010, 15(6), 4359-4368; doi:10.3390/molecules15064359
Received: 22 April 2010 / Revised: 22 May 2010 / Accepted: 26 May 2010 / Published: 15 June 2010
Cited by 5 | PDF Full-text (157 KB)
Abstract An efficient and convenient synthesis of pyrrolidinones and pyridinones utilizing enamino esters as starting material has been described. The structures of the compounds obtained were confirmed by spectral and elemental analyses. Full article
Open AccessArticle MALDI-TOF MS Analysis of Condensed Tannins with Potent Antioxidant Activity from the Leaf, Stem Bark and Root Bark of Acacia confusa
Molecules 2010, 15(6), 4369-4381; doi:10.3390/molecules15064369
Received: 26 May 2010 / Revised: 10 June 2010 / Accepted: 12 June 2010 / Published: 15 June 2010
Cited by 19 | PDF Full-text (276 KB)
Abstract
The structures of the condensed tannins from leaf, stem bark and root bark of Acacia confusa were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, and their antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric [...] Read more.
The structures of the condensed tannins from leaf, stem bark and root bark of Acacia confusa were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, and their antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing/antioxidant power (FRAP) assays. The results showed that the condensed tannins from stem bark and root bark include propelargonidin and procyanidin, and the leaf condensed tannins include propelargonidin, procyanidin and prodelphinidin, all with the procyanidin dominating. The condensed tannins had different polymer chain lengths, varying from trimers to undecamers for leaf and root bark and to dodecamers for stem bark. The condensed tannins extracted from the leaf, stem bark and root bark all showed a very good DPPH radical scavenging activity and ferric reducing power. Full article
Open AccessArticle Lead Generation and Optimization Based on Protein-Ligand Complementarity
Molecules 2010, 15(6), 4382-4400; doi:10.3390/molecules15064382
Received: 24 May 2010 / Accepted: 7 June 2010 / Published: 17 June 2010
Cited by 3 | PDF Full-text (1576 KB)
Abstract
This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in [...] Read more.
This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc). Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2), and c-Jun N-terminal kinase 3 (JNK3)). For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
Open AccessCommunication Preparation and Physicochemical Properties of the Complex of Naringenin with Hydroxypropyl-β-Cyclodextrin
Molecules 2010, 15(6), 4401-4407; doi:10.3390/molecules15064401
Received: 5 May 2010 / Revised: 7 June 2010 / Accepted: 9 June 2010 / Published: 18 June 2010
Cited by 18 | PDF Full-text (270 KB)
Abstract
In this study a complex of naringenin with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared to improve the hydrophilicity of naringenin. The physicochemical properties of the complex were analyzed by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC). The result [...] Read more.
In this study a complex of naringenin with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared to improve the hydrophilicity of naringenin. The physicochemical properties of the complex were analyzed by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC). The result showed that naringenin had been molecularly dispersed in the HP-β-CD matrix, not forming a new compound and HPLC analysis showed that the solubility of naringenin in water was enhanced from 4.38 μg/mL to 1,272.31 μg/mL. Full article
Open AccessArticle Synthesis of 2- and 7- Substituted C19 Steroids Having a 1,4,6-Triene or 1,4-Diene Structure and Their Cytotoxic Effects on T47D and MDA-MB231 Breast Cancer Cells
Molecules 2010, 15(6), 4408-4422; doi:10.3390/molecules15064408
Received: 25 May 2010 / Revised: 12 June 2010 / Accepted: 17 June 2010 / Published: 21 June 2010
Cited by 1 | PDF Full-text (2863 KB)
Abstract
2-Chloro-, 2-bromo- and 2-azido-1,4,6-androstatriene-3,17-diones were synthesized from 1α,2α-epoxy-4,6-androstadiene-3,17-dione (2) using HCl, HBr and NaN3, respectively. Compound 2 was also reacted with NaCN to give 2-cyano-1,4,6-androstatriene-3,17-dione (5) and 2β-cyano-1α-hydroxy-4,6-androstadiene-3,17-dione (6). 6α,7α-Epoxy-1,4-androstadiene-3,17-dione (8) was [...] Read more.
2-Chloro-, 2-bromo- and 2-azido-1,4,6-androstatriene-3,17-diones were synthesized from 1α,2α-epoxy-4,6-androstadiene-3,17-dione (2) using HCl, HBr and NaN3, respectively. Compound 2 was also reacted with NaCN to give 2-cyano-1,4,6-androstatriene-3,17-dione (5) and 2β-cyano-1α-hydroxy-4,6-androstadiene-3,17-dione (6). 6α,7α-Epoxy-1,4-androstadiene-3,17-dione (8) was reacted with HCl, HBr and NaN3 to form the corresponding 7β-chloro-, 7β-bromo- and 7β-azido-6α-hydroxy-1,4-androstadiene-3,17-diones. The cytotoxic activity of these compounds towards T47D (estrogen-dependent) and MDA-MB231 (estrogen-independent) breast cancer cell lines was evaluated. The 6α-hydroxy-7β-substituted analogs were more active than the 2-substituted analogs on both cell lines. Compound 2 showed the highest selective activity against the T47D (IC50 7.1 μM) cell line and 5 showed good cytotoxic activity on MDA-MB231 (IC50 18.5 μM) cell line, respectively. The 6α,7α-epoxy analog 8 also showed high cytotoxic activity on both cell lines (IC50 17.3 μM on T47D and IC50 26.9 μM on MDA-MB231). Full article
Open AccessArticle Synthesis of 2-(2-Aminopyrimidine)-2,2-difluoroethanols as Potential Bioisosters of Salicylidene Acylhydrazides
Molecules 2010, 15(6), 4423-4438; doi:10.3390/molecules15064423
Received: 19 May 2010 / Revised: 11 June 2010 / Accepted: 17 June 2010 / Published: 21 June 2010
Cited by 6 | PDF Full-text (234 KB)
Abstract
Salicylidene acylhydrazides are inhibitors of type III secretion in several Gram-negative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-amino-pyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to the [...] Read more.
Salicylidene acylhydrazides are inhibitors of type III secretion in several Gram-negative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-amino-pyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to the salicylidene acylhydrazide core structure. The synthesis of a library of 2-(2-amino-pyrimidine)-2,2-difluoro-ethanols is described in this paper. Full article
Open AccessArticle The Synthesis of Glycyrrhetinic Acid Derivatives Containing A Nitrogen Heterocycle and Their Antiproliferative Effects in Human Leukemia Cells
Molecules 2010, 15(6), 4439-4449; doi:10.3390/molecules15064439
Received: 4 May 2010 / Revised: 11 June 2010 / Accepted: 17 June 2010 / Published: 21 June 2010
Cited by 11 | PDF Full-text (274 KB)
Abstract
Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit [...] Read more.
Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit greater growth inhibitory effects, compared to those with a 2-hydroxymethylene-3-keto, an isoxazole, or a 2-cyano-3-keto group. N-(2-cyano-3,11-dioxoolean-1,12-dien-30-yl)-4-piperidyl piperidine (9b) was found to be two-fold more potent than methyl 2-cyano-3,11-dioxooleana-1,12- dien-30-oate(CDODO-Me-11). Full article
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Open AccessArticle HPLC and Anti-Inflammatory Studies of the Flavonoid Rich Chloroform Extract Fraction of Orthosiphon Stamineus Leaves
Molecules 2010, 15(6), 4452-4466; doi:10.3390/molecules15064452
Received: 13 April 2010 / Accepted: 4 May 2010 / Published: 21 June 2010
Cited by 29 | PDF Full-text (237 KB)
Abstract
The aim of the present study was to verify the anti-inflammatory activity of Orthosiphon stamineus leaf extracts and to identify the active compound(s) contributing to its anti-inflammatory activity using a developed HPLC method. Active chloroform extract of O. stamineus was fractionated into three fractions using a dry flash column chromatography method. These three fractions were investigated for anti-peritoneal capillary permeability, in vitro nitric oxide scavenging activity, anti-inflammatory and nitric oxide (NO) inhibition using carrageenan-induced hind paw edema method. The flavonoid rich chloroform extract fraction (CF2) [containing sinensetin (2.86% w/w), eupatorin (5.05% w/w) and 3’-hydroxy-5,6,7,4’-tetramethoxyflavone (1.101% w/w)], significantly reduced rat hind paw edema, NO and decreased dye leakage to peritoneal cavity at p < 0.05. IC50 of in vitro NO scavenging of CF2 was 0.3 mg/mL. These results suggest that the anti-inflammatory properties of these CF2 may possibly be due to the presence of flavonoid compounds capable of affecting the NO pathway. Full article
Open AccessArticle Antioxidant Properties of European Cranberrybush Fruit (Viburnum opulus var. edule)
Molecules 2010, 15(6), 4467-4477; doi:10.3390/molecules15064467
Received: 5 May 2010 / Revised: 22 June 2010 / Accepted: 22 June 2010 / Published: 23 June 2010
Cited by 22 | PDF Full-text (103 KB)
Abstract
In the literature there is little available information concerning European cranberrybush fruit (Viburnum opulus var. edule). This plant can be cultivated, even in harsh climatic conditions, because of its low environmental demands, and it is possible to harvest the fruit [...] Read more.
In the literature there is little available information concerning European cranberrybush fruit (Viburnum opulus var. edule). This plant can be cultivated, even in harsh climatic conditions, because of its low environmental demands, and it is possible to harvest the fruit even in the snow cover. The aim of this study was to determine the content of polyphenolics, antioxidant activity, flavonoids and vitamin C in the fruit of three cultivars ´Leningradskaya otbornaya´, ´Souzga´ and ´Taezny rubiny´ of this species. In the case of polyphenolics, high contents [up to 8.29 g of gallic acid/kg of fresh mass (FM)] were observed. The 1,1´-diphenyl-2-picrylhydrazyl (DPPH) and 2,2´-azinobis-3-ethyl-benzthiazino-6-sulphonic acid (ABTS) tests were applied to determine antioxidant activity, which was also high in comparison with other fruit species. The corresponding correlations between the polyphenolic content and antioxidant activity were in case of the DPPH test r2 = 0.88 and for the ABTS test r2 = 0.98. For comparison, the scavenging activity towards reactive oxygen species (superoxide anion, hydroxyl radical and nitric oxide) was determined by using a 25% fruit extract of particular cultivars. Antioxidant efficiency was also assessed using the rat liver slice model. Furthermore, the contents of flavonoids and vitamin C were assayed, giving values of 4.89 g/kg and 1.64 g/kg FM, respectively. The work should contribute to the popularization of this species as a promising crop plant in human nutrition. Full article
(This article belongs to the Special Issue Antioxidants)
Open AccessArticle In Vitro Antioxidant Activity and Hepatoprotective Effects of Lentinula edodes against Paracetamol-Induced Hepatotoxicity
Molecules 2010, 15(6), 4478-4489; doi:10.3390/molecules15064478
Received: 6 May 2010 / Revised: 9 June 2010 / Accepted: 10 June 2010 / Published: 23 June 2010
Cited by 21 | PDF Full-text (524 KB)
Abstract
Background: The objective of this study was to investigate the antioxidant and hepatoprotective effects of methanolic extracts of L. edodes and the determination of their total phenolics content. Results: The amount of total phenolics was estimated to be 70.83 mg Gallic Acid Equivalent (GAE) per gram of dry extract. The antioxidant activity of the L. edodes extract was 39.0% at a concentration of 1 mg/mL and was also concentration dependant, with an EC50 value of 4.4 mg/mL. Different groups of animals (Wister albino mice) were administered paracetamol (1 g/kg, p.o.). L. edodes extract at a dose of 200 mg/kg was administered to the paracetamol treated mice for seven days. The effects of L. edodes extract on serum transaminases (SGOT, SGPT), alkaline phosphatase (ALP) and bilirubin were measured in the paracetamol-induced hepatotoxic mice. L. edodes extract produced significant (p < 0.05) hepatoprotective effects by decreasing the activity of serum enzymes and bilirubin. Conclusions: From these results, it was suggested that L. edodes extract could perhaps protect liver cells from paracetamol-induced liver damage by its antioxidative effect on hepatocytes, hence diminishing or eliminating the harmful effects of toxic metabolites of paracetamol. Full article

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Open AccessReview Thiazolo[3,2-a]benzimidazoles: Synthetic Strategies, Chemical Transformations and Biological Activities
Molecules 2010, 15(6), 3775-3815; doi:10.3390/molecules15063775
Received: 8 April 2010 / Revised: 11 May 2010 / Accepted: 14 May 2010 / Published: 26 May 2010
Cited by 19 | PDF Full-text (383 KB)
Abstract The present review covers the recent synthetic strategies and chemical transformations of thiazolo[3,2-a]benzimidazoles and it also presents the highlights of the biological activities of these compounds. Full article
Open AccessReview Design and Use of Nanostructured Single-Site Heterogeneous Catalysts for the Selective Transformation of Fine Chemicals
Molecules 2010, 15(6), 3829-3856; doi:10.3390/molecules15063829
Received: 1 March 2010 / Revised: 10 May 2010 / Accepted: 24 May 2010 / Published: 26 May 2010
Cited by 34 | PDF Full-text (490 KB)
Abstract
Nanostructured single-site heterogeneous catalysts possess the advantages of classical solid catalysts, in terms of easy recovery and recycling, together with a defined tailored chemical and steric environment around the catalytically active metal site. The use of inorganic oxide supports with selected shape [...] Read more.
Nanostructured single-site heterogeneous catalysts possess the advantages of classical solid catalysts, in terms of easy recovery and recycling, together with a defined tailored chemical and steric environment around the catalytically active metal site. The use of inorganic oxide supports with selected shape and porosity at a nanometric level may have a relevant impact on the regio- and stereochemistry of the catalytic reaction. Analogously, by choosing the optimal preparation techniques to obtain spatially isolated and well-characterised active sites, it is possible to achieve performances that are comparable to (or, in the most favourable cases, better than) those obtained with homogeneous systems. Such catalysts are therefore particularly suitable for the transformation of highly-functionalised fine chemicals and some relevant examples where high chemo-, regio- and stereoselectivity are crucial will be described. Full article
(This article belongs to the Special Issue Heterogeneous Catalysis)
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Open AccessReview Processing of Polymer Nanocomposites Reinforced with Polysaccharide Nanocrystals
Molecules 2010, 15(6), 4111-4128; doi:10.3390/molecules15064111
Received: 12 May 2010 / Revised: 2 June 2010 / Accepted: 7 June 2010 / Published: 8 June 2010
Cited by 95 | PDF Full-text (244 KB)
Abstract
Aqueous suspensions of polysaccharide (cellulose, chitin or starch) nanocrystals can be prepared by acid hydrolysis of biomass. The main problem with their practical use is related to the homogeneous dispersion of these nanoparticles within a polymeric matrix. Water is the preferred processing [...] Read more.
Aqueous suspensions of polysaccharide (cellulose, chitin or starch) nanocrystals can be prepared by acid hydrolysis of biomass. The main problem with their practical use is related to the homogeneous dispersion of these nanoparticles within a polymeric matrix. Water is the preferred processing medium. A new and interesting way for the processing of polysaccharide nanocrystals-based nanocomposites is their transformation into a co-continuous material through long chain surface chemical modification. It involves the surface chemical modification of the nanoparticles based on the use of grafting agents bearing a reactive end group and a long compatibilizing tail. Full article
(This article belongs to the Special Issue Macromolecules: Chemistry, Medicinal and Functional Materials)
Open AccessReview Conazoles
Molecules 2010, 15(6), 4129-4188; doi:10.3390/molecules15064129
Received: 4 May 2010 / Accepted: 7 June 2010 / Published: 9 June 2010
Cited by 34 | PDF Full-text (510 KB)
Abstract
This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has [...] Read more.
This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described. Full article
(This article belongs to the Special Issue Anti-Infective Agents)
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Open AccessReview Construction of Eight-Membered Carbocycles with Trisubstituted Double Bonds Using the Ring Closing Metathesis Reaction
Molecules 2010, 15(6), 4242-4260; doi:10.3390/molecules15064242
Received: 21 May 2010 / Revised: 7 June 2010 / Accepted: 10 June 2010 / Published: 11 June 2010
Cited by 30 | PDF Full-text (1081 KB)
Abstract
Medium sized carbocycles are particularly difficult to synthesize. Ring closing metathesis reactions (RCM) have recently been applied to construct eight-membered carbocycles, but trisubstituted double bonds in the eight-membered rings are more difficult to produce using RCM reactions. In this review, model examples [...] Read more.
Medium sized carbocycles are particularly difficult to synthesize. Ring closing metathesis reactions (RCM) have recently been applied to construct eight-membered carbocycles, but trisubstituted double bonds in the eight-membered rings are more difficult to produce using RCM reactions. In this review, model examples and our own results are cited and the importance of the preparation of suitably designed precursors is discussed. Examples of RCM reactions used in the total synthesis of natural products are also outlined. Full article
(This article belongs to the Special Issue Ring-Closing Metathesis)
Open AccessReview Photochemical Oxidative Cyclisation of Stilbenes and Stilbenoids—The Mallory-Reaction
Molecules 2010, 15(6), 4334-4358; doi:10.3390/molecules15064334
Received: 2 April 2010 / Revised: 21 May 2010 / Accepted: 9 June 2010 / Published: 14 June 2010
Cited by 72 | PDF Full-text (294 KB)
Abstract
After Mallory described in 1964 the use of iodine as catalyst for the photochemical cyclisation of stilbenes, this reaction has proven its effectiveness in the synthesis of phenanthrenes, other PAHs and phenacenes with a surprisingly large selection of substituents. The “early age” [...] Read more.
After Mallory described in 1964 the use of iodine as catalyst for the photochemical cyclisation of stilbenes, this reaction has proven its effectiveness in the synthesis of phenanthrenes, other PAHs and phenacenes with a surprisingly large selection of substituents. The “early age” of the reaction was reviewed by Mallory in 1984in a huge chapter in the Organic Reactions series, but the development has continued. Alternative conditions accommodate more sensitive substituents, and isomers can be favoured by sacrificial substituents. Herein the further developments and applications of this reaction after 1984 are discussed and summarized. Full article
(This article belongs to the Special Issue Photochemistry in Organic Synthesis)
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