http://www.mdpi.com/journal/molecules Latest open access articles published in Molecules at http://www.mdpi.com/journal/molecules/ http://www.mdpi.com/1420-3049/15/3/1973/ Conjugate addition reaction of various nucleophiles across the vinyl group of 2-chloro-4-vinylpyrimidine, 2-chloro-4-(1-phenylvinyl)pyrimidine and 2-chloro-4-vinylquinazoline provides the corresponding 2-chloro-4-(2-substituted ethyl)pyrimidines and 2-chloro-4-(2-substituted ethyl)quinazolines. Treatment of these products, without isolation, with N-methylpiperazine results in nucleophilic displacement of chloride and yields the corresponding 2,4-disubstituted pyrimidines and quinazolines. http://www.mdpi.com/1420-3049/15/3/1973/ Fri, 19 Mar 2010 00:00:00 CET Molecules 2010-03-19 15 3 Article 1973 1984 1420-3049 Conjugate Addition of Nucleophiles to the Vinyl Function of 2-Chloro-4-vinylpyrimidine Derivatives 2010-03-19 doi: 10.3390/molecules15031973 Raux Klenc Blake Sączewski Strekowski http://www.mdpi.com/1420-3049/15/3/1967/ Quaternary pyridinium salts with chains ranging from C8 to C20 belong in the large group of cationic surfactants. In this paper, the preparation of such cationic surface active agents based on the pyridinium moiety and differing in the length of the N-alkyl chain is described. Additionally, HPLC technique was established to distinguish each prepared pyridinium analogue. This study represents universal method for preparation and identification of quaternary pyridinium detergents. http://www.mdpi.com/1420-3049/15/3/1967/ Fri, 19 Mar 2010 00:00:00 CET Molecules 2010-03-19 15 3 Communication 1967 1972 1420-3049 Preparation of the Pyridinium Salts Differing in the Length of the N-Alkyl Substituent 2010-03-19 doi: 10.3390/molecules15031967 Marek Stodulka Cabal Soukup Pohanka Korabecny Musilek Kuca http://www.mdpi.com/1420-3049/15/3/1958/ Using a cell-based cytotoxicity assay three new cytotoxic azaphilones, including two stereoisomers and designated monapurones A-C (1-3), were isolated from the extract of Monascus purpureus-fermented rice (red yeast rice). Their structures were elucidated by detailed interpretation of spectroscopic and chemical data. The relative configurations were assigned on the basis of analysis of NOE data, and the absolute configurations were determined by direct comparison of their CD spectra with those of known azaphilones and chemical correlations. In the in vitro assays, monapurones A-C (1-3) showed selective cytotoxicity against human cancer cell line A549 with IC50 values of 3.8, 2.8 and 2.4mM respectively, while exhibiting no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration. http://www.mdpi.com/1420-3049/15/3/1958/ Thu, 18 Mar 2010 00:00:00 CET Molecules 2010-03-18 15 3 Article 1958 1966 1420-3049 New Cytotoxic Azaphilones from Monascus purpureus-Fermented Rice (Red Yeast Rice) 2010-03-18 doi: 10.3390/molecules15031958 Li Shang Li Liu Zheng Jin http://www.mdpi.com/1420-3049/15/3/1932/ Lipid vesicles spontaneously fuse and assemble into a lipid bilayer on planar or spherical silica surfaces and other substrates. The supported lipid bilayers (SLBs) maintain characteristics of biological membranes, and are thus considered to be biomembrane mimetic systems that are stable because of the underlying substrate. Examples of their shared characteristics with biomembranes include lateral fluidity, barrier formation to ions and molecules, and their ability to incorporate membrane proteins into them. Biomimetic silica microspheres consisting of SLBs on solid or porous silica microspheres have been utilized for different biosensing applications. The advantages of such biomimetic microspheres for biosensing include their increased surface area to volume ratio which improves the detection limits of analytes, and their amenability for miniaturization, multiplexing and high throughput screening. This review presents examples and formats of using such biomimetic solid or porous silica microspheres in biosensing. http://www.mdpi.com/1420-3049/15/3/1932/ Wed, 17 Mar 2010 00:00:00 CET Molecules 2010-03-17 15 3 Review 1932 1957 1420-3049 Biomimetic Silica Microspheres in Biosensing 2010-03-17 doi: 10.3390/molecules15031932 Chemburu Fenton Lopez Zeineldin http://www.mdpi.com/1420-3049/15/3/1918/ In this manuscript, we report clear evidence for the generation of aromatic cation radicals produced by using [hydroxy(tosyloxy)iodo]benzene (HTIB) in fluoroalcohol solvents such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). The single-electron-transfer (SET) oxidation ability of HTIB to give cation radicals was first established by ESR and UV measurements. The reaction was broadly applied to various thiophenes, and unique thienyliodonium salts were directly synthesized by this method in excellent yields without the production of any harmful byproducts. http://www.mdpi.com/1420-3049/15/3/1918/ Wed, 17 Mar 2010 00:00:00 CET Molecules 2010-03-17 15 3 Article 1918 1931 1420-3049 Enhanced Reactivity of [Hydroxy(tosyloxy)iodo]benzene in Fluoroalcohol Media. Efficient Direct Synthesis of Thienyl(aryl)iodonium Salts 2010-03-17 doi: 10.3390/molecules15031918 Ito Ogawa Yamaoka Fujioka Dohi Kita http://www.mdpi.com/1420-3049/15/3/1903/ Styrylquinoline derivatives are demonstrated to be HIV-1 integrase inhibitors. On the basis of our previous CoMFA analysis of a series of styrylquinoline derivatives, N-[(2-substituted-styryl)-5-chloro-8-hydroxyquinolin-7-yl]-benzenesulfonamide derivatives were designed and synthesized,and their possible HIV IN inhibitory activity was evaluated. http://www.mdpi.com/1420-3049/15/3/1903/ Tue, 16 Mar 2010 00:00:00 CET Molecules 2010-03-16 15 3 Article 1903 1917 1420-3049 Design, Synthesis and Anti-HIV Integrase Evaluation of N-(5-Chloro-8-Hydroxy-2-Styrylquinolin-7-yl)Benzenesulfonamide Derivatives 2010-03-16 doi: 10.3390/molecules15031903 Jiao He Zeng Tan Hu Wang http://www.mdpi.com/1420-3049/15/3/1898/ The focus of this paper was to identify a cheaper solvent from among diesel fuel, kerosene, sulfolane or a mixture of sulfolane and cyclohexanol for the preparation of cyanuric acid heterocyclization of urea. To obtain a higher yield, the effects of catalyst (sodium, ammonium, calcium and zinc salts) and temperature (160 °C to 220 °C) on the trimerization of urea were also carefully studied. We established the optimal reaction conditions and further validated them in our scale-up experiments. http://www.mdpi.com/1420-3049/15/3/1898/ Tue, 16 Mar 2010 00:00:00 CET Molecules 2010-03-16 15 3 Article 1898 1902 1420-3049 Liquid-Phase Synthesis of Cyanuric Acid from Urea 2010-03-16 doi: 10.3390/molecules15031898 She Yu Huang Li Li http://www.mdpi.com/1420-3049/15/3/1891/ A new triterpenoid saponin was isolated from Pulsatilla cernua, along with eight known triterpenoids and triterpenoid glycosides. The new compound was identified as 3-O-β-D-glucopyranosyl-(1→4)-α-L-arabinopyranosyl-bayogenin-28-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (1) on the basis of 1D, 2D-NMR techniques, including COSY, HMBC, and HMQC correlations, MS analysis, as well as chemical methods. http://www.mdpi.com/1420-3049/15/3/1891/ Tue, 16 Mar 2010 00:00:00 CET Molecules 2010-03-16 15 3 Communication 1891 1897 1420-3049 A New Triterpenoid Saponin from Pulsatilla cernua 2010-03-16 doi: 10.3390/molecules15031891 Xu Bai Liu Liu Xu Xie Si Zhou Liu Xu http://www.mdpi.com/1420-3049/15/3/1882/ A variety of novel bicyclic and tricyclic pyrimidine derivatives was obtained via reaction of 6-amino-2-thioxo-1H-pyrimidine-4-one (1) with a different reagents. The antimicrobial and anti-inflammatory activities of some of the synthesized compounds were tested. http://www.mdpi.com/1420-3049/15/3/1882/ Mon, 15 Mar 2010 00:00:00 CET Molecules 2010-03-15 15 3 Article 1882 1890 1420-3049 Synthesis of Certain Pyrimidine Derivatives as Antimicrobial Agents and Anti-Inflammatory Agents 2010-03-15 doi: 10.3390/molecules15031882 Mohamed Awad Sayed http://www.mdpi.com/1420-3049/15/3/1873/ Many studies indicate that traditional Chinese herbs are beneficial in the prevention and treatment of cardiovascular diseases. Evodia rutaecarpa (‘Wu-Chu-Yu’)remains the most popular and multi-purpose herb traditionally used in China for treatment of headache, abdominal pain, postpartum hemorrhage, dysentery and amenorrhea. Rutaecarpine is one of the intriguing indolopyridoquinazoline alkaloids isolated from ‘Wu-Chu-Yu’. Rutaecarpine has been shown to have cardiovascular biological effects such as inotropic and chronotropic, vasorelaxant, anti-platelet aggregation and anti-inflammatory effects. Furthermore, it has been reported that rutaecarpine has beneficial effects on some cardiovascular diseases. This review summarizes data on the cardiovascular pharmacological actions of rutaecarpine the published over the recent years, aiming to provide more evidence supporting its use in the treatment of cardiovascular diseases. http://www.mdpi.com/1420-3049/15/3/1873/ Mon, 15 Mar 2010 00:00:00 CET Molecules 2010-03-15 15 3 Review 1873 1881 1420-3049 Pharmacological Effects of Rutaecarpine as a Cardiovascular Protective Agent 2010-03-15 doi: 10.3390/molecules15031873 Jia Hu http://www.mdpi.com/1420-3049/15/3/1825/ The role of vitamin A and its metabolites in the life processes starting with the historical background and its up to date information is discussed in the introduction. Also the role of 11Z-retinal in vision and retinoic acid in the biological processes is elucidated. The essential role of isotopically enriched systems in the progress of vision research, nutrition research etc. is discussed. In part B industrial commercial syntheses of vitamin A by the two leading companies Hoffmann-La Roche (now DSM) and BASF are discussed. The knowledge obtained via these pioneering syntheses has been essential for the further synthetic efforts in vitamin A field by other scientific groups. The rest of the paper is devoted to the synthetic efforts of the Leiden group that gives an access to the preparation of site directed high level isotope enrichment in retinals. First the synthesis of the retinals with deuterium incorporation in the conjugated side chain is reviewed. Then, 13C-labeled retinals are discussed. This is followed by the discussion of a convergent synthetic scheme that allows a rational access to prepare any isotopomer of retinals. The schemes that provide access to prepare any possible isotope enriched chemically modified systems are discussed. Finally, nor-retinals and bridged retinals that give access to a whole (as yet incomplete) library of possible isotopomers are reviewed. http://www.mdpi.com/1420-3049/15/3/1825/ Mon, 15 Mar 2010 00:00:00 CET Molecules 2010-03-15 15 3 Review 1825 1872 1420-3049 Synthesis and Use of Stable Isotope Enriched Retinals in the Field of Vitamin A 2010-03-15 doi: 10.3390/molecules15031825 Dawadi Lugtenburg http://www.mdpi.com/1420-3049/15/3/1811/ Antimicrobial activity and cytotoxicity of fifty one extracts of different parts of 14 plants were studied. Ethanol, methanol, aqueous, butanol, and n-hexane extracts were tested against three Gram negative, two Gram positive bacteria, and two fungi. Cytotoxicity and phytochemical screening were determined using MTT and TLC assays, respectively. Of the fifty one extracts, twenty two showed activities against different microorganisms with MICs ranging from 62.5 to 1000 µg/mL. The highest activity (100% inhibition) was for a butanol extract of Rosa damascena receptacles against Salmonella typhimurium and Bacillus cereus (MIC of 62.5 and 250 µg/mL) respectively. Butanol extract of Narcissus tazetta aerial parts and aqueous extract of Rosa damascena receptacles were both active against Candida albicans (MIC of 125 µg/mL). Methicillin-resistant Staphylococcus aureus was inhibited by butanol, aqueous extracts of Rosa damascena receptacles and butanol extract of Inula viscosa flowers (MIC of 500, 500, and 250 µg/mL) respectively. Rosa damascena receptacles and Verbascum sinaiticum flowers ethanol extract showed lowest cytoxicity against Vero cell line (IC50 of 454.11and 367.11). Most toxic was the ethanol extract of Ononis hirta aerial parts (IC50 72.50 µg/mL). Flavonoids and terpenoids were present in all plants. Ononis hirta and Narcissus tazetta contained alkaloids. The results validate the use of these plants and report for the first time bioactivity of Rosa damascena receptacles and further justifies the use of such screening programs in the quest for new drugs. http://www.mdpi.com/1420-3049/15/3/1811/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Article 1811 1824 1420-3049 Antimicrobial, Cytotoxicity and Phytochemical Screening of Jordanian Plants Used in Traditional Medicine 2010-03-12 doi: 10.3390/molecules15031811 Talib Mahasneh http://www.mdpi.com/1420-3049/15/3/1798/ A new macromolecule possessing two dansyl moieties and based on 2-[4-(2-aminoethylthio)butylthio]ethanamine was prepared as a fluorescent sensor and its mercury sensing properties toward various transition metal, alkali, and alkali earth ions were investigated. The designed compound exhibited pronounced Hg2+-selective ON-OFF type fluorescence switching upon binding. The new compoundprovided highly selective sensing to Hg2+ in acetonitrile-water solvent mixtures with a detection limit of 2.49 x 10-7 M or 50 ppb. The molecular modeling results indicated that ions-recognition of the sensor originated from a self assembly process of the reagentand Hg2+ to form a helical wrapping structure with the favorable electrostatic interactions of Hg2+coordinated with sulfur, oxygen, nitrogen atoms and aromatic moieties. http://www.mdpi.com/1420-3049/15/3/1798/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Article 1798 1810 1420-3049 Synthesis of a Novel Fluorescent Sensor Bearing Dansyl Fluorophores for the Highly Selective Detection of Mercury (II) Ions 2010-03-12 doi: 10.3390/molecules15031798 Wanichacheva Watpathomsub Lee Grudpan http://www.mdpi.com/1420-3049/15/3/1784/ Organotin monomers containing dibutyltin groups – dibutyltin citraconate (DBTC) as a new monomer and dibutyltin maleate (DBTM) – were synthesized. Free radical copolymerizations of the organotin monomers with styrene (ST) and butyl acrylate (BA) were performed. The overall conversion was kept low (≤15% wt/wt) for all studied samples and the copolymers composition was determined from tin analysis using the Gillman and Rosenberg method. The reactivity ratios were calculated from the copolymer composition using the Fineman-Ross (FR) method. The synthesized monomers were characterized by elemental analysis, 1H-, 13C-NMR and FTIR spectroscopy. http://www.mdpi.com/1420-3049/15/3/1784/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Article 1784 1797 1420-3049 Synthesis and Characterization of Organotin Containing Copolymers: Reactivity Ratio Studies 2010-03-12 doi: 10.3390/molecules15031784 Al-Deyab Al-Hazmi El-Newehy http://www.mdpi.com/1420-3049/15/3/1762/ Prostate cancer (PC) is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Here we review the relationship of vitamins to PC risk. Many vitamins and related chemicals, including vitamin A, retinoids, several B vitamins, vitamin C, vitamin D and vitamin E have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed these vitamins may have anti-PC properties, whether they can effectively prevent the development and/or progression of PC in humans remains to be intensively studied subjects. This review will provide up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of vitamins on PC prevention and/or treatment. http://www.mdpi.com/1420-3049/15/3/1762/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Review 1762 1783 1420-3049 Vitamins and Prostate Cancer Risk 2010-03-12 doi: 10.3390/molecules15031762 Donkena Karnes Young http://www.mdpi.com/1420-3049/15/3/1746/ Vitamin E is an essential vitamin and a lipid soluble antioxidant, at least, under in vitro conditions. The antioxidant properties of vitamin E are exerted through its phenolic hydroxyl group, which donates hydrogen to peroxyl radicals, resulting in the formation of stable lipid species. Beside an antioxidant role, important cell signalling properties of vitamin E have been described. By using gene chip technology we have identified α-tocopherol sensitive molecular targets in vivo including christmas factor (involved in the blood coagulation) and 5α-steroid reductase type 1 (catalyzes the conversion of testosterone to 5α-dihydrotestosterone) being upregulated and γ-glutamyl-cysteinyl synthetase (the rate limiting enzyme in GSH synthesis) being downregulated due to a-tocopherol deficiency. α-Tocopherol regulates signal transduction cascades not only at the mRNA but also at the miRNA level since miRNA 122a (involved in lipid metabolism) and miRNA 125b (involved in inflammation) are downregulated by α-tocopherol. Genetic polymorphisms may determine the biological and gene-regulatory activity of a-tocopherol. In this context we have recently shown that genes encoding for proteins involved in peripheral α-tocopherol transport and degradation are significantly affected by the apoE genotype. http://www.mdpi.com/1420-3049/15/3/1746/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Review 1746 1761 1420-3049 Gene-Regulatory Activity of α-Tocopherol 2010-03-12 doi: 10.3390/molecules15031746 Rimbach Moehring Huebbe Lodge http://www.mdpi.com/1420-3049/15/3/1722/ Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives. http://www.mdpi.com/1420-3049/15/3/1722/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Review 1722 1745 1420-3049 Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview 2010-03-12 doi: 10.3390/molecules15031722 Alfini Cecchi Giomi http://www.mdpi.com/1420-3049/15/3/1705/ Despite international efforts to ‘roll back malaria’ the 2008 World Malaria Report revealed the disease still affects approximately 3 billion people in 109 countries; 45 within the WHO African region. The latest report however does provide some ‘cautious optimism’; more than one third of malarious countries have documented greater than 50% reductions in malaria cases in 2008 compared to 2000. The goal of the Member States at the World Health Assembly and ‘Roll Back Malaria’ (RBM) partnership is to reduce the numbers of malaria cases and deaths recorded in 2000 by 50% or more by the end of 2010. Although malaria is preventable it is most prevalent in poorer countries where prevention is difficult and prophylaxis is generally not an option. The burden of disease has increased by the emergence of multi drug resistant (MDR) parasites which threatens the use of established and cost effective antimalarial agents. After a major change in treatment policies, artemisinins are now the frontline treatment to aid rapid clearance of parasitaemia and quick resolution of symptoms. Since artemisinin and its derivatives are eliminated rapidly, artemisinin combination therapies (ACT’s) are now recommended to delay resistance mechanisms. In spite of these precautionary measures reduced susceptibility of parasites to the artemisinin-based component of ACT’s has developed at the Thai-Cambodian border, a historical ‘hot spot’ for MDR parasite evolution and emergence. This development raises serious concerns for the future of the artemsinins and this is not helped by controversy related to the mode of action. Although a number of potential targets have been proposed the actual mechanism of action remains ambiguous. Interestingly, artemisinins have also shown potent and broad anticancer properties in cell lines and animal models and are becoming established as anti-schistosomal agents. In this review we will discuss the recent evidence explaining bioactivation and potential molecular targets in the chemotherapy of malaria and cancer. http://www.mdpi.com/1420-3049/15/3/1705/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Review 1705 1721 1420-3049 The Molecular Mechanism of Action of Artemisinin—The Debate Continues 2010-03-12 doi: 10.3390/molecules15031705 O’Neill Barton Ward http://www.mdpi.com/1420-3049/15/3/1690/ West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 µM final concentration was conducted using the 384-well format. Z′ values ranged from 0.54–0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively. http://www.mdpi.com/1420-3049/15/3/1690/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Article 1690 1704 1420-3049 HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity 2010-03-12 doi: 10.3390/molecules15031690 Chung Jonsson Maddox McKellip Moore Heil White Ananthan Li Feng Rasmussen http://www.mdpi.com/1420-3049/15/3/1679/ In this study we investigated the antimicrobial activity of magnolol on Staphylococcus aureus. The minimal inhibitory concentrations of magnolol against 31 S. aureus strains ranged from 4–32 μg/mL. In addition, hemolysin assays, Western blotting, and real-time RT-PCR were performed to investigate the effect of magnolol on α-toxin secretion by both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The results indicated that sub-inhibitory concentrations of magnolol dose-dependently inhibited the transcription of hla (the gene encoding α-toxin) in S. aureus, resulting in a reduction of α-toxin secretion and, thus, hemolytic activities. http://www.mdpi.com/1420-3049/15/3/1679/ Fri, 12 Mar 2010 00:00:00 CET Molecules 2010-03-12 15 3 Article 1679 1689 1420-3049 Influence of Magnolol on the Secretion of α-Toxin by Staphylococcus aureus 2010-03-12 doi: 10.3390/molecules15031679 Xiang Qiu Wang Jiang Xia Deng http://www.mdpi.com/1420-3049/15/3/1668/ Investigations were carried out to determine antimicrobial and antioxidant properties and total phenol content of three wild species of Ephedra compared with their respective callus cultures. Callus induction was performed in a standard Murashige and Skoog (MS) medium with the following hormonal ranges (mg/L) for every species NAA:1.5, Kin:1 for Ephedra strobiliacea, NAA:2, Kin:1 for Ephedra procera and NAA:2, Kin:0.5 for Ephedra pachyclada. These ranges of PGPR (Plant Growth Promote Regulators) were chosen based on callus induction rates, RGR (Relative Growth Rate) and their fresh weights. An antimicrobial test against five Gram negative and two Gram positive bacteria and two fungi was performed using the disc diffusion method. All methanolic extracts showed antimicrobial activity, but the antimicrobial activity of the callus cultures was lower than those of the wild plants. E. strobilacea showed the highest antimicrobial activity, and all methanolic extracts of the wild plants and callus cultures unexpectedly showed the highest antimicrobial activity against Pseudomonas aeruginosa. A FRAP (Ferric Reducing Antioxidant Power) test was conducted to evaluate extracts for antioxidant activity. E. strobilacea with 1.61 ± 0.08 mmol eq quercetin/gextract and 0.278 ± 0.02 mmol eq quercetin/gextract for the wild plant and callus, respectively, showed the highest results.The total phenol content of extracts was measured by a Folin Ciocalteau test. All the chosen species displayed phenol contents but E. strobilacea had the highest amount (504.9 ± 41.51 μmol eq catechin/gextracts and 114.61 ± 15.13 μmol eq catechin/gextracts for the wild plants and callus, respectively). http://www.mdpi.com/1420-3049/15/3/1668/ Thu, 11 Mar 2010 00:00:00 CET Molecules 2010-03-11 15 3 Article 1668 1678 1420-3049 A Comparative Study of the Antibacterial, Antifungal and Antioxidant Activity and Total Content of Phenolic Compounds of Cell Cultures and Wild Plants of Three Endemic Species of Ephedra 2010-03-11 doi: 10.3390/molecules15031668 Ali Parsaeimehr Elmira Sargsyan Katayoun Javidnia http://www.mdpi.com/1420-3049/15/3/1645/ We instituted a quasi-quality assurance program for demonstrating coniferyl alcohol’s fluorescence and fluorescence diminishment following enzymatic oxidation. The magnitude of diminishment was a measure of catalysis. High throughput screening was performed in pseudo-kinetic and endpoint modes by measuring the fluorescence at 416 nm following excitation at 290, 310 or 340 nm. Dose-response tracings were linear between two and three orders of magnitude with average limits of detection and quantitation of 1.8 and 6.9 mM coniferyl alcohol, respectively. Oxidation was evident with 0.025 mg/mL laccase or 0.003 mg/mL peroxidase or inside 5 min using 0.5 mg/mL laccase or 5 mM substrate. Sodium chloride inhibited (IC50, 25 mM) laccase oxidation of coniferyl alcohol. Fluorescence from 10 concentrations (1 to 1000 mM) of coniferyl alcohol was stable for 24 hours over 14 excitation/emission cycles at 3 different combinations of excitation and emission wavelengths. In conclusion, coniferyl alcohol absorption and fluorescence assays should facilitate biomass lignin analyses and improve delignification. http://www.mdpi.com/1420-3049/15/3/1645/ Thu, 11 Mar 2010 00:00:00 CET Molecules 2010-03-11 15 3 Article 1645 1667 1420-3049 Hitherto Unrecognized Fluorescence Properties of Coniferyl Alcohol 2010-03-11 doi: 10.3390/molecules15031645 Komandoor Elayavalli Achyuthan Paul David Adams Supratim Datta Blake Alexander Simmons Anup Kumar Singh http://www.mdpi.com/1420-3049/15/3/1632/ Folic acid plays an important role in neuronal development. A series of newly synthesized bioactive compounds (NSCs) was reported to exhibit immunoactive and neuroprotective functions. The isolated and combined effects of folic acid and NSCs against β-amyloid (Aβ)-induced cytotoxicity are poorly understood. These effects were tested using human microglia cells (C13NJ) subjected to Aβ(25-35) challenge. According to an MTT assay, treatment of C13NJ cells with Aβ(25-35) at 10~100 μM for 48 h induced 18%~43% cellular death in a dose-dependent manner (p < 0.05). Aβ(25-35) treatment at 25 μM induced nitrite oxide (NO) release, elevated superoxide production, and reduced the distribution of cells in the S phase. Preincubation of C13NJ with 100 μM folic acid protected against Aβ(25-35)-induced cell death, which coincided with a reduction in NO release by folic acid supplements. NSC47 at a level of 50 μM protected against Aβ(25-35)-induced cell death and reduced Aβ-promoted superoxide production (p < 0.05). Folic acid in combination with NSC47 at their cytoprotective doses did not synergistically ameliorate Aβ(25-35)-associated NO release, superoxide production, or cell cycle arrest. Taken together, folic acid or NSC treatment alone, but not the combined regimen, protected against Aβ(25-35)-induced cell death, which may partially, if not completely, be mediated by free radical-scavenging effects. http://www.mdpi.com/1420-3049/15/3/1632/ Thu, 11 Mar 2010 00:00:00 CET Molecules 2010-03-11 15 3 Article 1632 1644 1420-3049 The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(25-35)-Induced Toxicity in Human Microglial Cells 2010-03-11 doi: 10.3390/molecules15031632 Yih-Fong Liew Chao-Tzu Huang Shang-Shing P. Chou Yuh-Chi Kuo Shiu-Huey Chou Jyh-Yih Leu Woan-Fang Tzeng Su-Jane Wang Ming-Chi Tang Rwei-Fen Syu Huang http://www.mdpi.com/1420-3049/15/3/1590/ Combinatorial chemistry is a powerful tool used to rapidly generate a large number of potentially biologically active compounds. In our goal to develop bisubstrate inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) that interact with both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding sites, we used parallel solid-phase synthesis to prepare three libraries of 16β-estradiol derivatives with two or three levels of molecular diversity. From estrone, we first synthesized a sulfamate precursor that we loaded on trityl chloride resin using the efficient multidetachable sulfamate linker strategy recently developed in our laboratory. We then introduced molecular diversity [one or two amino acid(s) followed by a carboxylic acid] on steroid nucleus by Fmoc peptide chemistry. Finally, after a nucleophilic cleavage, libraries of 30, 63 and 25 estradiol derivatives were provided. A library of 30 sulfamoylated estradiol derivatives was also generated by acidic cleavage and its members were screened for inhibition of steroid sulfatase. Biological evaluation on homogenated HEK-293 cells overexpressing 17β-HSD1 of the estradiol derivatives carrying different oligoamide-type chains at C-16 first revealed that three levels of molecular diversity (a spacer of two amino acids) were necessary to interact with the adenosine part of the cofactor binding site. Second, the best inhibition was obtained when hydrophobic residues (phenylalanine) were used as building blocks. http://www.mdpi.com/1420-3049/15/3/1590/ Wed, 10 Mar 2010 00:00:00 CET Molecules 2010-03-10 15 3 Article 1590 1631 1420-3049 Preparation of 16β-Estradiol Derivative Libraries as Bisubstrate Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Using the Multidetachable Sulfamate Linker 2010-03-10 doi: 10.3390/molecules15031590 Marie Bérubé Florian Delagoutte Donald Poirier http://www.mdpi.com/1420-3049/15/3/1578/ Complexes between oxovanadium (IV) cation and flavonoid derivatives were developed recently in order to increase the intestinal absorption and to reduce the toxicity of vanadium compounds. For these reasons, is interesting to investigate the complexation process between flavonoid rutin (Rut) and vanadyl cation in order to isolate new complexes. Two new complexes [VO(Rut)(H2O)2](SO4)0.5×2H2O and [VO(Rut)2]×4H2O have been obtained and characterized by elemental and thermal analyses and several spectroscopic techniques (ESI-MS, IR, UV-Vis, fluorescence). The studies concerning complex formation between vanadyl and rutin (Rut) performed in different solutions show the formation of mononuclear complexes with 1:1 and 1:2 metal to ligand stoichiometry. http://www.mdpi.com/1420-3049/15/3/1578/ Wed, 10 Mar 2010 00:00:00 CET Molecules 2010-03-10 15 3 Article 1578 1589 1420-3049 Synthesis, Spectral and Thermal Studies of New Rutin Vanadyl Complexes 2010-03-10 doi: 10.3390/molecules15031578 Valentina Uivarosi Stefania Felicia Barbuceanu Victoria Aldea Corina-Cristina Arama Mihaela Badea Rodica Olar Dana Marinescu http://www.mdpi.com/1420-3049/15/3/1562/ Inula britannica L., family Asteraceae, is used in traditional Chinese and Kampo Medicines for various diseases. Flowers or the aerial parts are a rich source of secondary metabolites. These consist mainly of terpenoids (sesquiterpene lactones and dimmers, diterpenes and triterpenoids) and flavonoids. The isolated compounds have shown diverse biological activities: anticancer, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective activities. This review provides information on isolated bioactive phytochemicals and pharmacological potentials of I. britannica. http://www.mdpi.com/1420-3049/15/3/1562/ Wed, 10 Mar 2010 00:00:00 CET Molecules 2010-03-10 15 3 Review 1562 1577 1420-3049 Secondary Metabolites from Inula britannica L. and Their Biological Activities 2010-03-10 doi: 10.3390/molecules15031562 Abdul Latif Khan Javid Hussain Muhammad Hamayun Syed Abdullah Gilani Shabir Ahmad Gauhar Rehman Yoon-Ha Kim Sang-Mo Kang In-Jung Lee http://www.mdpi.com/1420-3049/15/3/1554/ We have identified through bioassay guided isolation an allelochemical, eudesmane-type sesquiterpeniod, 3β-caffeoxyl-β1,8α-dihydroxyeudesm-4(15)-ene(1),from an endemic plant species growing in the Himalayas. In our search for the bioactive subfraction, the hexane one was highly significant, showing 100% inhibition of lettuce seed growth at 100 ppm while other subfractions (chloroform, ethyl acetate, butanol and water) exhibited inhibitory to stimulatory allelopathic effects. The bioactive hexane subfraction was subjected to chromatographic techniques, using lettuce seeds (Lactuca sativa) as indicator species to reveal the bioactive allelopathic fraction. This resulted in the isolation of compound 1, whose structure was elucidated through NMR techniques. The compound presented 92.34% inhibitory effect on the growth of lettuce at 500 ppm. Further field level experiments may help develop an environmentally friendly herbicide from this lead. http://www.mdpi.com/1420-3049/15/3/1554/ Wed, 10 Mar 2010 00:00:00 CET Molecules 2010-03-10 15 3 Communication 1554 1561 1420-3049 Allelochemical, Eudesmane-Type Sesquiterpenoids from Inula falconeri 2010-03-10 doi: 10.3390/molecules15031554 Abdul Latif Khan Javid Hussain Muhammad Hamayun Sang-Mo Kang Hak-Youn Kim Kazuo N. Watanabe In-Jung Lee http://www.mdpi.com/1420-3049/15/3/1531/ Aerobic and anaerobic respiratory systemsallow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents. http://www.mdpi.com/1420-3049/15/3/1531/ Wed, 10 Mar 2010 00:00:00 CET Molecules 2010-03-10 15 3 Review 1531 1553 1420-3049 Vitamin K2 in Electron Transport System: Are Enzymes Involved in Vitamin K2 Biosynthesis Promising Drug Targets? 2010-03-10 doi: 10.3390/molecules15031531 Michio Kurosu Eeshwaraiah Begari http://www.mdpi.com/1420-3049/15/3/1513/ The thermal [4+2] cycloadditions of 3-acetyl-, 3-carbamoyl, and 3-ethoxycarbonylcoumarins with 2,3-dimethyl-1,3-butadiene under solvent free conditions are reported, as well as the epoxidation reactions of some adducts. Discussion is focused on the structural features of the Diels-Alder adducts and their epoxides, based upon NMR, X-ray, and mass spectral data, and supported by ab initio theoretical calculations. http://www.mdpi.com/1420-3049/15/3/1513/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1513 1530 1420-3049 Thermal [4 + 2] Cycloadditions of 3-Acetyl-, 3-Carbamoyl-, and 3-Ethoxycarbonyl-Coumarins with 2,3-Dimethyl-1,3-butadiene under Solventless Conditions: A Structural Study 2010-03-09 doi: 10.3390/molecules15031513 Irma Y. Flores-Larios Lizbeth López-Garrido Francisco J. Martínez-Martínez Jorge González Efrén V. García-Báez Alejandro Cruz Itzia I. Padilla-Martínez http://www.mdpi.com/1420-3049/15/3/1501/ The synthesis of a new chiral pyrrolidine has been performed using 2,3-O-isopropylidene-D-erythronolactol as a suitable starting material. http://www.mdpi.com/1420-3049/15/3/1501/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1501 1512 1420-3049 Synthesis of a New Chiral Pyrrolidine 2010-03-09 doi: 10.3390/molecules15031501 Mari Fe. Flores Marta G. Núñez Rosalina F. Moro Narciso M. Garrido Isidro S. Marcos Enrique F. Iglesias Pilar García David Díez http://www.mdpi.com/1420-3049/15/3/1487/ The direct aerobic coupling reaction of arenes with olefins was successfully achieved by the use of Pd(OAc)2/molybdovanadophosphoric acid (HPMoV) as a key catalyst under 1 atm of dioxygen. This catalytic system could be extended to the coupling reaction of various substituted benzenes with olefins such as acrylates, aclrolein, and ethylene through the direct aromatic C-H bond activation. http://www.mdpi.com/1420-3049/15/3/1487/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Review 1487 1500 1420-3049 Pd(II)/HPMoV-Catalyzed Direct Oxidative Coupling Reaction of Benzenes with Olefins 2010-03-09 doi: 10.3390/molecules15031487 Yasushi Obora Yasutaka Ishii http://www.mdpi.com/1420-3049/15/3/1473/ Coprinus comatus, also called chicken drumstick mushroom, is currently commercially available in China. Hot water and ethanolic extracts were prepared from cap and stipe of C. comatus fruit bodies and their antioxidant properties were studied. Ethanolic extract from stipe showed high antioxidant activity (80.6%) at 1 mg/mL. Reducing power of hot water extracts from cap was 1.653 at 10 mg/mL. Extracts from cap showed better scavenging ability on DPPH (57.9% at 1 mg/mL) than stipe ones. Ethanolic extracts were more effective in scavenging ability on hydroxyl radicals (57.4–61.3% at 5 mg/mL) than hot water extracts. Ethanolic extracts showed moderate scavenging ability on superoxide radicals (46.3–47.0% at 20 mg/mL). Naturally occurring antioxidant components including total phenols (3.60–20.00 mg/g), tocopherols (0.58–11.93 mg/g), flavonoids (0.19–3.52 mg/g) and polysaccharides (58.52–547.86 mg/g) were found in the extracts. Overall, extracts from cap were more effective for the antioxidant properties assayed. http://www.mdpi.com/1420-3049/15/3/1473/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1473 1486 1420-3049 Antioxidant Properties of Cap and Stipe from Coprinus comatus 2010-03-09 doi: 10.3390/molecules15031473 Bo Li Fei Lu Xiaomin Suo Haijuan Nan Bin Li http://www.mdpi.com/1420-3049/15/3/1466/ The oxidation of 1-unsubstituted or 1-phenyl-1H-isotellurochromenes with m-chloroperbenzoic acid (mCPBA) in CHCl3 resulted in a ring opening reaction to produce as the sole products the corresponding o-formyl or benzoyl distyryl ditellurides, which were also produced by the hydrolysis of the 2-benzotelluropyrylium salts readily prepared from the parent isotellurochromene. http://www.mdpi.com/1420-3049/15/3/1466/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1466 1472 1420-3049 Novel Oxidative Ring Opening Reaction of 1H-Isotelluro-chromenes to Bis(o-formylstyryl) Ditellurides 2010-03-09 doi: 10.3390/molecules15031466 Haruki Sashida Hirohito Satoh Kazuo Ohyanagi Mamoru Kaname http://www.mdpi.com/1420-3049/15/3/1453/ Nephelium lappaceum is a tropical fruit whose peel possesses antioxidant properties. Experiments on the isolation and identification of the active constituents were conducted, and on their antioxidant activity using a lipid peroxidation inhibition assay. The methanolic extract of N. lappaceum peels exhibited strong antioxidant properties. Sephadex LH-20 chromatography was utilized in the isolation of each constituent and the antioxidant properties of each was studied. The isolated compounds were identified as ellagic acid (EA) (1), corilagin (2) and geraniin (3). These compounds accounted for 69.3% of methanolic extract, with geraniin (56.8%) as the major component, and exhibited much greater antioxidant activities than BHT in both lipid peroxidation (77-186 fold) and DPPH• (42-87 fold) assays. The results suggest that the isolated ellagitannins, as the principal components of rambutan peels, could be further utilized as both a medicine and in the food industry. http://www.mdpi.com/1420-3049/15/3/1453/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1453 1465 1420-3049 Identification of Major Phenolic Compounds from Nephelium lappaceum L. and Their Antioxidant Activities 2010-03-09 doi: 10.3390/molecules15031453 Nont Thitilertdecha Aphiwat Teerawutgulrag Jeremy D. Kilburn Nuansri Rakariyatham http://www.mdpi.com/1420-3049/15/3/1442/ A novel chiral macrocyclic ligand incorporating a chiral salen moiety into a framework containing two biphenyl units was synthesized. Structural properties and conformational aspects of the free ligand and an UO2 complex were studied by using NMR spectroscopy in solution and MM calculations. The Mn(III) complex was tested as catalyst in enantioselective oxidation of prochiral unfunctionalized olefins to the corresponding optically active epoxides under very mild conditions. http://www.mdpi.com/1420-3049/15/3/1442/ Tue, 09 Mar 2010 00:00:00 CET Molecules 2010-03-09 15 3 Article 1442 1452 1420-3049 Synthesis and Conformational Study of a Novel Macrocyclic Chiral(Salen) ligand and its Uranyl and Mn Complexes 2010-03-09 doi: 10.3390/molecules15031442 Maria E. Amato Francesco P. Ballistreri Andrea Pappalardo Gaetano A. Tomaselli Rosa M. Toscano http://www.mdpi.com/1420-3049/15/3/1433/ SrCl2·6H2O has been shown to act as an efficient catalyst for the conversion of aldehydes or ketones into the corresponding gem-dihydroperoxides (DHPs) by treatment with aqueous H2O2 (30%) in acetonitrile. The reactions proceed under mild and neutral conditions at room temperature to afford good to excellent yields of product. http://www.mdpi.com/1420-3049/15/3/1433/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Article 1433 1441 1420-3049 Mild and Efficient Strontium Chloride Hexahydrate-Catalyzed Conversion of Ketones and Aldehydes into Corresponding gem- Dihydroperoxides by Aqueous H2O2 2010-03-08 doi: 10.3390/molecules15031433 Davood Azarifar Kaveh Khosravi Fatemeh Soleimanei http://www.mdpi.com/1420-3049/15/3/1425/ New organotin substituted α-anilinomethylphosphonates were prepared and were characterized by FT-IR, 1H- and 13C-NMR spectroscopy and elemental microanalysis. http://www.mdpi.com/1420-3049/15/3/1425/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Article 1425 1432 1420-3049 Synthesis and Characterization of Novel Organotin-Phosphorous Compounds II 2010-03-08 doi: 10.3390/molecules15031425 Salem S. Al-Deyab Mohamed H. El-Newehy http://www.mdpi.com/1420-3049/15/3/1408/ Development of effective and environmentally friendly disinfectants, or virucidal agents, should help prevent the spread of infectious diseases through human contact with contaminated surfaces. These agents may also be used, if non-toxic to cells and tissues, as chemotherapeutic agents against infectious diseases. We have shown that arginine has a synergistic effect with a variety of virucidal conditions, namely acidic pH and high temperature, on virus inactivation. All of these treatments are effective, however, at the expense of toxicity. The ability of arginine to lower the effective threshold of these parameters may reduce the occurrence of potential toxic side effects. While it is clear that arginine can be safely used, the mechanism of its virus inactivation has not yet been elucidated. Here we examine the damages that viruses suffer from various physical and chemical stresses and their relations to virus inactivation and aggregation. Based on the relationship between the stress-induced structural damages and the infectivity of a virus, we will propose several plausible mechanisms describing the effects of arginine on virus inactivation using the current knowledge of aqueous arginine solution properties. http://www.mdpi.com/1420-3049/15/3/1408/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Review 1408 1424 1420-3049 Arginine as a Synergistic Virucidal Agent 2010-03-08 doi: 10.3390/molecules15031408 Satoshi Ohtake Tsutomu Arakawa A. Hajime Koyama http://www.mdpi.com/1420-3049/15/3/1398/ The cationic ring-opening polymerization reaction of tetrahydrofuran at 20 ºC was catalyzed by H3PW12O40·13H2O as solid acid catalyst. The effect of the proportions of acetic anhydride and catalyst, reaction time and support on the polymerization reaction was investigated. It has been found that the yield and the viscosity of the polymer depend on the proportion of acetic anhydride, the presence of the latter in the reactant mixture being required for the ring-opening. The catalytic activity of the alumina-supported heteropolyacid results showed that Brønsted acid sites are more effective than Lewis ones for the cationic ring-opening polymerization. http://www.mdpi.com/1420-3049/15/3/1398/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Article 1398 1407 1420-3049 The Cationic Ring-Opening Polymerization of Tetrahydrofuran with 12-Tungstophosphoric Acid 2010-03-08 doi: 10.3390/molecules15031398 Ahmed Aouissi Salem S. Al-Deyab Hassan Al-Shahri http://www.mdpi.com/1420-3049/15/3/1378/ Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA), as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work. http://www.mdpi.com/1420-3049/15/3/1378/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Review 1378 1397 1420-3049 Biological Actions of Artemisinin: Insights from Medicinal Chemistry Studies 2010-03-08 doi: 10.3390/molecules15031378 Jian Li Bing Zhou http://www.mdpi.com/1420-3049/15/3/1354/ New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A1 (PLA1), A2 (PLA2) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo-enzymatic procedures leading to 1- and 2-LPLs will be described. http://www.mdpi.com/1420-3049/15/3/1354/ Mon, 08 Mar 2010 00:00:00 CET Molecules 2010-03-08 15 3 Review 1354 1377 1420-3049 Synthesis of Lysophospholipids 2010-03-08 doi: 10.3390/molecules15031354 Paola D’Arrigo Stefano Servi http://www.mdpi.com/1420-3049/15/3/1340/ A novel method for the conversion of unprotected and unmodified aldoses to aldo-imidazoles has been developed. Using iodine as a catalyst in acetic acid solution, a series of mono- and oligosaccharides, including those containing carboxyl and acetamido groups, undergo an oxidative condensation reaction with aromatic vicinal diamines at room temperature to give the corresponding aldo-imidazole products in high yields. No cleavage of the glycosidic bond occurs under the mild reaction conditions. The compositional analysis of saccharides is commonly realized by capillary electropheresis of the corresponding aldo-imidazole derivatives, which are easily synthesized by the reported iodine-promoted oxidative condensation. In addition, a series of aldo-imidazoles were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) to analyze molecular weight and ion intensity. The diamine-labeled saccharides showed enhanced signals in MALDI–TOF MS. The combined use of aldoimidazole derivatization and mass spectrometric analysis thus provides a rapid method for identification of saccharides, even when less than 1 pmol of saccharide is present in the sample. These results can be further applied to facilitate the isolation and analysis of novel saccharides. http://www.mdpi.com/1420-3049/15/3/1340/ Fri, 05 Mar 2010 00:00:00 CET Molecules 2010-03-05 15 3 Article 1340 1353 1420-3049 I2-Catalyzed Oxidative Condensation of Aldoses with Diamines: Synthesis of Aldo-Naphthimidazoles for Carbohydrate Analysis 2010-03-05 doi: 10.3390/molecules15031340 Chunchi Lin Wei-Ting Hung Chien-Yuan Kuo Kuo-Shiang Liao Yin-Chen Liu Wen-Bin Yang http://www.mdpi.com/1420-3049/15/3/1324/ A series of Ru(II) and Os(II) tris-chelate complexes with new bidentate 2-pyridylquinoline ligands have been synthesized and fully characterized by EA,1H-NMR and FAB-MS techniques. The new ligands are: L1 = 4-p-methoxyphenyl-6-bromo-2-(2′- pyridyl)quinoline (mphbr-pq) and L2 = 4-p-hydroxyphenyl-6-bromo-2-(2′-pyridyl)-quinoline (hphbr-pq). The complexes studied are: [Ru(bpy)2L1](PF6)2 (C1), [Ru(bpy)2L2](PF6)2 (C2), [Os(bpy)2L1](PF6)2 (C3), [Os(bpy)2L2](PF6)2 (C4) (bpy = 2,2′-bipyridine), [Ru(dmbpy)2L1](PF6)2 (C5), [Ru(dmbpy)2L2](PF6)2 (C6), [Os(dmbpy)2L1](PF6)2 (C7), and [Os(dmbpy)2L2](PF6)2 (C8) (dmbpy = 4,4′-dimethyl-2,2′-bipyridine). Moreover, new functionalized complexes C9-C12 were obtained by the basecatalyzed direct alkylation of C2, C4, C6, and C8 with 6-bromo-1-hexene. The complete assignment of the 1H-NMR spectra for the two new ligands (L1 and L2), and their Ru(II) or Os(II) complexes has been accomplished using a combination of one- and two-dimensional NMR techniques. The JH,H values have been determined for the majority of the resonances. http://www.mdpi.com/1420-3049/15/3/1324/ Fri, 05 Mar 2010 00:00:00 CET Molecules 2010-03-05 15 3 Article 1324 1339 1420-3049 Asymmetric Ruthenium(II) and Osmium(II) Complexes with New Bidentate Polyquinoline Ligands. Synthesis and NMR Characterization 2010-03-05 doi: 10.3390/molecules15031324 Antonino Mamo Alessandro Aureliano Antonino Recca http://www.mdpi.com/1420-3049/15/3/1309/ Since its identification in the early 1970s, artemisinin, as well as semi-synthetic derivatives and synthetic trioxanes, have been used in malaria therapy. Reduction of artemisinin by NaBH4 produced dihydroartemisinin (DHA), and yielded a new stereochemically labile centre at C-10, which, in turn, provided two interconverting lactol hemiacetal epimers (namely a and b), whose rate of interconversion depends on buffer, pH, and solvent polarity. Since interconversion of the two epimers occurred on a chromatographic time-scale, this prompted a thorough investigation of the phenomenon as a crucial requisite of any analytical method aimed at quantitating this family of drugs. In this critical review we discuss the current importance of the on-column epimerization of DHA in the development of analytical methods aimed at quantifying the drug, with the purpose of identifying the optimal conditions to minimize on-column epimerization while achieving the best selectivity and efficiency of the overall separation. http://www.mdpi.com/1420-3049/15/3/1309/ Fri, 05 Mar 2010 00:00:00 CET Molecules 2010-03-05 15 3 Review 1309 1323 1420-3049 Stereodynamic Investigation of Labile Stereogenic Centres in Dihydroartemisinin 2010-03-05 doi: 10.3390/molecules15031309 Ilaria D’Acquarica Francesco Gasparrini Dorina Kotoni Marco Pierini Claudio Villani Walter Cabri Michela Di Mattia Fabrizio Giorgi http://www.mdpi.com/1420-3049/15/3/1302/ The palladium-catalyzed hydroarylation of N-methyl-substituted tricyclic imides was studied in order to find a new stereoselective access to a series of new exo-aryl(hetaryl)-substituted tricyclic N-methylimides. http://www.mdpi.com/1420-3049/15/3/1302/ Thu, 04 Mar 2010 00:00:00 CET Molecules 2010-03-04 15 3 Article 1302 1308 1420-3049 Reductive Heck Reactions of N-Methyl-substituted Tricyclic Imides 2010-03-04 doi: 10.3390/molecules15031303 Gokce Goksu Nuket Ocal Dieter E. Kaufmann http://www.mdpi.com/1420-3049/15/3/1291/ The reduction of γ-N-benzylamino-β-ketophosphonates 6 and 10, readily available from L-proline and L-serine, respectively, can be carried out in high diastereoselectivity with catecholborane (CB) in THF at -78 ºC to produce the syn-γ-N-benzylamino-β-hydroxyphosphonates 11 and 13 as a single detectable diastereoisomer, under non-chelation or Felkin-Anh model control. http://www.mdpi.com/1420-3049/15/3/1291/ Thu, 04 Mar 2010 00:00:00 CET Molecules 2010-03-04 15 3 Article 1291 1301 1420-3049 Synthesis of syn-γ-Amino-β-hydroxyphosphonates by Reduction of β-Ketophosphonates Derived from L-Proline and L-Serine 2010-03-04 doi: 10.3390/molecules15031291 Mario Ordóñez Selene Lagunas-Rivera Emanuel Hernández-Núñez Victoria Labastida-Galván http://www.mdpi.com/1420-3049/15/3/1280/ A catalytic asymmetric nitro-Mannich (aza-Henry) reaction with rare earth metal/alkali metal heterobimetallic catalysts is described. A Yb/K heterobimetallic catalyst assembled by an amide-based ligand promoted the asymmetric nitro-Mannich reaction to afford enantioenriched anti-b-nitroamines in up to 86% ee. Facile reduction of the nitro functionality allowed for efficient access to optically active 1,2-diamines. http://www.mdpi.com/1420-3049/15/3/1280/ Thu, 04 Mar 2010 00:00:00 CET Molecules 2010-03-04 15 3 Article 1280 1290 1420-3049 Catalytic Asymmetric Nitro-Mannich Reactions with a Yb/K Heterobimetallic Catalyst 2010-03-04 doi: 10.3390/molecules15031280 Tatsuya Nitabaru Naoya Kumagai Masakatsu Shibasaki http://www.mdpi.com/1420-3049/15/3/1270/ Both bifidobacteria and clostridia are part of the natural gut microflora and while clostridia may be responsible for severe intestinal infections, bifidobacteria are probiotic microorganisms belonging to the most important prospective bacteria in the bowel. The antimicrobial activity of biochanin A was tested in vitro against six Bifidobacterium spp., and eight Clostridium spp. using the broth microdilution method. Biochanin A showed an inhibition against all clostridia in the range of minimum inhibitory concentrations (MIC) from 64 μg/mL (for Cl. clostridioforme, strains DSM 933 and I3) to 1,024 μg/mL (for Cl. perfringens, DSM 11778). No bifidobacteria were suppressed at four-fold higher concentration (MICs > 4,096) than MIC of Cl. perfringens. These results indicate selective growth inhibition of biochanin A and its potential use in antimicrobial prevention and/or protection. http://www.mdpi.com/1420-3049/15/3/1270/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Communication 1270 1279 1420-3049 Selective Growth Inhibitory Effect of Biochanin A Against Intestinal Tract Colonizing Bacteria 2010-03-03 doi: 10.3390/molecules15031270 Olga Sklenickova Jaroslav Flesar Ladislav Kokoska Eva Vlkova Katerina Halamova Jan Malik http://www.mdpi.com/1420-3049/15/3/1242/ Reduced glutathione (GSH) is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation and apoptosis. GSH deficiency has been observed in aging and in a wide range of pathologies, including neurodegenerative disorders and cystic fibrosis (CF), as well as in several viral infections. Use of GSH as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. Several reports have provided evidence for the use of GSH prodrugs able to replenish intracellular GSH levels. This review discusses different strategies for increasing GSH levels by supplying reversible bioconjugates able to cross the cellular membrane more easily than GSH and to provide a source of thiols for GSH synthesis. http://www.mdpi.com/1420-3049/15/3/1242/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Review 1242 1264 1420-3049 Prodrug Approach for Increasing Cellular Glutathione Levels 2010-03-03 doi: 10.3390/molecules15031242 Ivana Cacciatore Catia Cornacchia Francesco Pinnen Adriano Mollica Antonio Di Stefano http://www.mdpi.com/1420-3049/15/3/1265/ Lithium, used in conjunction with sodium metal, produces a high yield of biphenyl when reacted with dibenzothiophene, dibenzothiophene sulfoxide or dibenzothiophene sulfone. http://www.mdpi.com/1420-3049/15/3/1265/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Article 1265 1269 1420-3049 Desulfurization of Dibenzothiophene and Oxidized Dibenzothiophene Ring Systems 2010-03-03 doi: 10.3390/molecules15031265 Diego P. Morales Alexander S. Taylor Steven C. Farmer http://www.mdpi.com/1420-3049/15/3/1232/ Research over the past decade has indicated that melanocortin peptides are potent inhibitors of inflammation and a promising source of new anti-inflammatory and cytoprotective therapies. The purpose of the present paper is to compare protective effects of α-, β-, and γ-melanocyte stimulating hormone on acetaminophen induced liver lesions in male CBA mice. Acetaminophen was applied intragastrically in a dose of 150 mg/kg, and tested substances were applied intraperitoneally 1 hour before acetaminophen. Mice were sacrificed after 24 hours and intensity of liver injury was estimated by measurement of plasma transaminase activity (AST and ALT) and histopathological grading of lesions. It was found that α-, β-, and γ-MSH decrease intensity of lesions by both criteria in a dose-dependent manner. http://www.mdpi.com/1420-3049/15/3/1232/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Article 1232 1241 1420-3049 The Influence of α-, β-, and γ-Melanocyte Stimulating Hormone on Acetaminophen Induced Liver Lesions in Male CBA Mice 2010-03-03 doi: 10.3390/molecules15031232 Vladimir Blagaić Karlo Houra Petra Turčić Nikola Štambuk Paško Konjevoda Alenka Boban-Blagaić Tomislav Kelava Marina Kos Gorana Aralica Filip Čulo http://www.mdpi.com/1420-3049/15/3/1223/ The in vitro antiradical activity of Schisandra chinensis lignans was investigated using DPPH, ABTS+, Fenton reaction inhibition and tyrosine-nitration inhibition assays, as were the in vivo antidiabetic activities of selected lignans in an animal model of alloxan-induced diabetes. Different degrees of antiradical activity were found, depending upon the structural parameters of the tested compounds. Unfortunately, the compounds showed no antidiabetic activity in concentration range tested. http://www.mdpi.com/1420-3049/15/3/1223/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Article 1223 1231 1420-3049 Evaluation of the Antiradical Activity of Schisandra Chinensis Lignans Using Different Experimental Models 2010-03-03 doi: 10.3390/molecules15031223 Karel Šmejkal Tereza Šlapetová Pavel Krmenčík Renata Kubínová Pavel Suchý Stefano Dall´Acqua Gabbriella Innocenti Ján Vančo Karolína Kalvarová Margita Dvorská Jiří Slanina Eva Kramářová Jan Muselík Milan Žemlička http://www.mdpi.com/1420-3049/15/3/1213/ The association constants Kb of three hosts I–III designed to have both enhanced hydrogen bonding donor strength and conformational preorganization with biotin analogues 1–5 are reported. 1H-NMR titrations under two different concentration conditions have been employed to determine the association constants Kb. A statistical analysis using a presence absence matrix has been applied to calculate the different contributions. Hydrogen bond interactions make naphthyridine derivatives II and III potent binders and effective receptors for (+)-biotin methyl ester (1), due to the complex stabilization by additional hydrogen bonds. http://www.mdpi.com/1420-3049/15/3/1213/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Article 1213 1222 1420-3049 Molecular Recognition Studies on Naphthyridine Derivatives 2010-03-03 doi: 10.3390/molecules15031213 José Carlos Iglesias-Sánchez Dolores Santa María Rosa M. Claramunt José Elguero http://www.mdpi.com/1420-3049/15/3/1196/ Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES) have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES’s chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES’s phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties. http://www.mdpi.com/1420-3049/15/3/1196/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Review 1196 1212 1420-3049 trans-Resveratrol as A Neuroprotectant 2010-03-03 doi: 10.3390/molecules15031196 Ellen L. Robb Jeffrey A. Stuart http://www.mdpi.com/1420-3049/15/3/1168/ Both acute and chronic degenerative diseases of the nervous system reduce the viability and function of neurons through changes in intracellular calcium signaling. In particular, pathological increases in the intracellular calcium concentration promote such pathogenesis. Disease involvement of numerous regulators of intracellular calcium signaling located on the plasma membrane and intracellular organelles has been documented. Diverse groups of chemical compounds targeting ion channels, G-protein coupled receptors, pumps and enzymes have been identified as potential neuroprotectants. The present review summarizes the discovery, mechanisms and biological activity of neuroprotective molecules targeting proteins that control intracellular calcium signaling to preserve or restore structure and function of the nervous system. Disease relevance, clinical applications and new technologies for the identification of such molecules are being discussed. http://www.mdpi.com/1420-3049/15/3/1168/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Review 1168 1195 1420-3049 Control of Intracellular Calcium Signaling as a Neuroprotective Strategy 2010-03-03 doi: 10.3390/molecules15031168 R. Scott Duncan Daryl L. Goad Michael A. Grillo Simon Kaja Andrew J. Payne Peter Koulen http://www.mdpi.com/1420-3049/15/3/1161/ A new geldanamycin analogue was isolated from Streptomyces hygroscopicus A070101. The structure was elucidated as 11-methoxy-17-formyl-17-demethoxy-18-O-21-O-dihydrogeldanamycin (1) on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. Compound 1 showed considerable cytotoxicity (SRB) against human cancer cell lines (breast cancer MCF-7, skin melanoma SK-MEL-2 and lung carcinoma COR-L23). http://www.mdpi.com/1420-3049/15/3/1161/ Wed, 03 Mar 2010 00:00:00 CET Molecules 2010-03-03 15 3 Communication 1161 1167 1420-3049 A New Geldanamycin Analogue from Streptomyces hygroscopicus 2010-03-03 doi: 10.3390/molecules15031161 Hao Zhang Guang-Zhi Sun Xiang Li Hong-Yu Pan Yan-Sheng Zhang http://www.mdpi.com/1420-3049/15/3/1154/ (S)-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields. http://www.mdpi.com/1420-3049/15/3/1154/ Tue, 02 Mar 2010 00:00:00 CET Molecules 2010-03-02 15 3 Article 1154 1160 1420-3049 Copper-Catalyzed N-Arylation of Amides Using (S)-N-Methylpyrrolidine-2-carboxylate as the Ligand 2010-03-02 doi: 10.3390/molecules15031154 Chaoyu Wang Lijuan Liu Wei Wang Dong-Sheng Ma Hua Zhang http://www.mdpi.com/1420-3049/15/3/1141/ Yan73 is a “teinturier” red wine variety cultivated in China and used in winemaking to strengthen red wine color. Here, the anthocyanin profile in both the skin and pulp of this grape variety was analyzed by HPLC-MS. The results showed that 18 anthocyanins were detected in both the skin and the pulp, and pelargonidin-3-O-glucoside, an anthocyanin compound hardly detected in most other Vitis viniferaberries, was found. However, the contents of individual anthocyanins in the skin and the pulp were significantly different. Compared with the skin, the pulp exhibited much lower ratio of 3’,5’-substituted to 3’-substituted anthocyanins and much higher ratio of methoxylation of anthocyanin B-ring to non methoxylation, and with regard to the aromatic acylated and aliphatic acylated anthocyanins, both their contents in the skin are higher than in the pulp. The findings will provide some new insight for the tissue-specific expression and regulation of the genes involving in anthocyanin biosynthesis in grape berries. http://www.mdpi.com/1420-3049/15/3/1141/ Tue, 02 Mar 2010 00:00:00 CET Molecules 2010-03-02 15 3 Article 1141 1153 1420-3049 Different Anthocyanin Profiles of the Skin and the Pulp of Yan73 (Muscat Hamburg × Alicante Bouschet) Grape Berries 2010-03-02 doi: 10.3390/molecules15031141 Jian-Jun He Yan-Xia Liu Qiu-Hong Pan Xiang-Yun Cui Chang-Qing Duan http://www.mdpi.com/1420-3049/15/3/1127/ We have selected aptamers binding to lysozyme from a DNA library using capillary electrophoresis-systematic evolution of ligands by exponential enrichment. During the selection process the dissociation constant of the ssDNA pool decreased from the micromolar to the low nanomolar range within five rounds of selection. The final aptamer had a dissociation constant of 2.8 ± 0.3 nM, 6.1 ± 0.5 nM, and 52.9 ± 9.1 nM as determined by fluorescence anisotropy, surface plasmon resonance and affinity capillary electrophoresis respectively. The aptamers were successfully challenged for specificity against other egg white proteins. The high affinity aptamers open up possibilities for the development of aptamer based food and medical diagnostics. http://www.mdpi.com/1420-3049/15/3/1127/ Tue, 02 Mar 2010 00:00:00 CET Molecules 2010-03-02 15 3 Article 1127 1140 1420-3049 Selection and Characterization of DNA Aptamers for Egg White Lysozyme 2010-03-02 doi: 10.3390/molecules15031127 Dinh T. Tran Kris P. F. Janssen Jeroen Pollet Elke Lammertyn Jozef Anné Ann Van Schepdael Jeroen Lammertyn http://www.mdpi.com/1420-3049/15/3/1113/ The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC) and 4-dimethylaminopyridine (DMAP) was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pKa ~ 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa ~ 8) furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroaryl)sulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroaryl)sulfonyl isocyanates. http://www.mdpi.com/1420-3049/15/3/1113/ Fri, 26 Feb 2010 00:00:00 CET Molecules 2010-02-26 15 3 Article 1113 1126 1420-3049 Synthesis of Novel Aryl(heteroaryl)sulfonyl Ureas of Possible Biological Interest 2010-02-26 doi: 10.3390/molecules15031113 Franciszek Sączewski Anna Kuchnio Monika Samsel Marta Łobocka Agnieszka Kiedrowska Karolina Lisewska Jarosław Sączewski Maria Gdaniec Patrick J. Bednarski http://www.mdpi.com/1420-3049/15/3/1103/ Compoundswith two phenolic OH groups like curcumin possess efficient antioxidant and anti-inflammatory activity. We synthesized p-cresol dimer (2,2'-dihydroxy-5,5'-dimethylbiphenol, 2a) and p-methoxyphenol dimer (2,2'-dihydroxy-5,5'-dimethoxybiphenol, 2b) by ortho-ortho coupling reactions of the parent monomers, p-cresol (1a) and p-methoxyphenol (1b), respectively. Their antioxidant activity was determined using the induction period method, and their cytotoxicity towards RAW 264.7 cells was also investigated using a cell counting kit. The stoichiometric factors n (number of free radicals trapped by one mole of antioxidant moiety) for 2a and 2b were 3 and 2.8, respectively, being greater than those for 1a and 1b. The ratio of the rate constant of inhibition to that of propagation (kinh/kp) for 2a and 2b was similar to that for 2-t-butyl-4-methoxyphenol (BHA), a conventional food antioxidant. The 50% inhibitory dose (ID50) declined in the order 1b > 1a >> 2b > 2a > BHA. The cytotoxicity for 2a and 2b was significantly greater than that for the parent monomers (p < 0.001), but smaller than that for BHA (p < 0.01). Compounds 2a and 2b may be useful as food antioxidants. http://www.mdpi.com/1420-3049/15/3/1103/ Fri, 26 Feb 2010 00:00:00 CET Molecules 2010-02-26 15 3 Article 1103 1112 1420-3049 Radical-Scavenging Activity and Cytotoxicity of p-Methoxyphenol and p-Cresol Dimers 2010-02-26 doi: 10.3390/molecules15031103 Yoshinori Kadoma Yukio Murakami Takako Ogiwara Mamoru Machino Ichiro Yokoe Seiichiro Fujisawa http://www.mdpi.com/1420-3049/15/3/1097/ A new flavone, named crotoncaudatin (1), was isolated from the stems of Croton caudatus Geisel. var. tomentosus Hook., together with nine known analogues: 3,5,6,7,8,3′,4′-heptamethoxyflavone (2), tangeretin (3), nobiletin (4), 5,6,7,4′-tetramethoxy-flavone (5), sinensetin (6), kaempferol (7), tiliroside (8), kaempferol-3-O-rutinoside (9) and rutin (10). The structures of the above compounds were established by a combination of spectroscopic methods, including HR-ESI-MS, 1H-NMR, 13C-NMR, HMQC and HMBC spectra. All compounds were isolated from and identified in this species for the first time and compounds 1-6 are new for the genus Croton. http://www.mdpi.com/1420-3049/15/3/1097/ Fri, 26 Feb 2010 00:00:00 CET Molecules 2010-02-26 15 3 Article 1097 1102 1420-3049 Flavonoids from the Stems of Croton caudatus Geisel. var. tomentosus Hook 2010-02-26 doi: 10.3390/molecules15031097 Guo-An Zou Zhi-Heng Su Hong-Wu Zhang Yuan Wang Jun-Shan Yang Zhong-Mei Zou http://www.mdpi.com/1420-3049/15/2/1089/ Two new polyynes, named oplopantriol A (5) and oplopantriol B (6), were isolated from the root bark of Oplopanax horridus (Smith) Miq, an ethnic medicinal plant of North America, along with four known polyynes: (3S,8S)-falcarindiol (1), oplopandiol (2), (11S,16S,9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol, 1-acetate (3) and oplopandiol acetate (4). The structures of the new compounds were elucidated by detailed spectroscopic analyses, including 1D and 2D NMR techniques and chemical methods. The absolute configurations of the new compounds 5 and 6 were determined by comparing their optical rotation values with the hydrolysis products of the known compounds 3 and 4, respectively, derived from the same plant. On the basis of an analysis of their physical and chemical properties we show that the alkaline hydrolysis of 3 and 4 afforded the new compounds 5 and 6, respectively. http://www.mdpi.com/1420-3049/15/2/1089/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 1089 1096 1420-3049 Isolation and Identification of Two New Polyynes from a North American Ethnic Medicinal Plant--Oplopanax horridus (Smith) Miq. 2010-02-23 doi: 10.3390/molecules15021089 Wei-Hua Huang Qing-Wen Zhang Chong-Zhi Wang Chun-Su Yuan Shao-Ping Li http://www.mdpi.com/1420-3049/15/2/1082/ Because of their interesting biological properties various methods for the synthesis of substituted pyrroles are described in the literature. However, synthesis of pyrroles fused with a β-lactam ring has not been reported. Our group has demonstrated synthesis and biological evaluation of various β-lactams as anticancer agents. The anticancer activities of these compounds have prompted us to study the synthesis of pyrroles bound to the β-lactams. We have identified an expeditious synthetic method for the preparation of pyrroles fused with β-lactams by reacting 3-amino β-lactams with acetonylacetone in the presence of catalytic amounts (5 mol%) of molecular iodine at room temperature. It has also been discovered that the reaction gives products under domestic and automated microwave oven irradiation. To our knowledge, there are no other prior reports that describe the synthesis of pyrrole-substituted β-lactams. http://www.mdpi.com/1420-3049/15/2/1082/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Communication 1082 1088 1420-3049 Remarkable Iodine-Catalyzed Synthesis of Novel Pyrrole- Bearing N-Polyaromatic β-Lactams 2010-02-23 doi: 10.3390/molecules15021082 Debasish Bandyopadhyay Gildardo Rivera Isabel Salinas Hector Aguilar Bimal K. Banik http://www.mdpi.com/1420-3049/15/2/1074/ Ten novel 4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxy acetates and 4-(4,6-dimethylpyrimidin-2-yloxy)phenoxy acetates were synthesized with hydroquinone, 2-methylsulfonyl-4,6-disubstituted-pyrimidine and chloroacetic ester as starting materials. The products were characterized by IR, 1H-NMR, MS spectra and elemental analyses. Preliminary bioassay indicates that the target compounds possess high herbicidal activity against monocotyledonous plants such as Digitaria sanguinalis L. at concentrations of 100 mg/L and 50 mg/L. http://www.mdpi.com/1420-3049/15/2/1074/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 1074 1081 1420-3049 Synthesis and Biological activity of 4-(4,6-Disubstituted-pyrimidin-2-yloxy)phenoxy Acetates 2010-02-23 doi: 10.3390/molecules15021074 Lin Jiang Hao Wang Maorong Wang Xinhuan Teng http://www.mdpi.com/1420-3049/15/2/1041/ An overview of the synthesis and applications of chiral 2,3-epoxy alcohols containing unsaturated chains is presented. One of the fundamental synthetic routes to these compounds is Sharpless asymmetric epoxidation, which is reliable, highly chemoselective and enables easy prediction of the product enantioselectivity. Thus, unsaturated epoxy alcohols are readily obtained by selective oxidation of the allylic double bond in the presence of other carbon-carbon double or triple bonds. The wide availability of epoxy alcohols with unsaturated chains, the versatility of the epoxy alcohol functionality (e.g. regio- and stereo-selective ring opening; oxidation; and reduction), and the arsenal of established alkene chemistries, make unsaturated epoxy alcohols powerful starting materials for the synthesis of complex targets such as biologically active molecules. The popularization of ring-closing metathesis has further increased their value, making them excellent precursors to cyclic compounds. http://www.mdpi.com/1420-3049/15/2/1041/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Review 1041 1073 1420-3049 Synthetic Applications of Chiral Unsaturated Epoxy Alcohols Prepared by Sharpless Asymmetric Epoxidation 2010-02-23 doi: 10.3390/molecules15021041 Antoni Riera María Moreno http://www.mdpi.com/1420-3049/15/2/1028/ Novel Ru(II) complex-based hybrid inorganic-organic materials immobilized via a diamine co-ligand site instead of the conventional diphosphine ligand have been prepared. The complexes were prepared by two different methods: sol-gel and surface modification techniques. The structures of the desired materials were deduced by several available physical measurements like elemental analyses, infrared, FAB-MS and 1H-, 13C- and 31P-NMR spectroscopy. Due to a lack of solubility the structures of xerogel 3 and modified 4 were studied by solid state 13C-, 29Si- and 31P-NMR spectroscopy, infrared spectroscopy and EXAFS. These materials were stable enough to serve as hydrogenation catalysts. Selective hydrogenation of functionalized carbonyls in a,b-unsaturated compounds was successfully carried out under mild conditions in a basic medium using these complexes as catalysts. http://www.mdpi.com/1420-3049/15/2/1028/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 1028 1040 1420-3049 Synthesis and Characterization of Novel Inorganic-Organic Hybrid Ru(II) Complexes and Their Application in Selective Hydrogenation 2010-02-23 doi: 10.3390/molecules15021028 Ismail Warad Zeid Al-Othman Saud Al-Resayes Salem S. Al-Deyab El-Refaie Kenawy http://www.mdpi.com/1420-3049/15/2/1007/ Medical-grade polyvinyl chloride was coated by polysaccharides through a novel physicochemical approach. An initial surface activation was performed foremost via diffuse coplanar surface barrier discharge plasma in air at ambient temperature and pressure. Then, radical graft copolymerization of acrylic acid through grafting-from pathway was directed to render a well-defined brush of high density, and finally a chitosan monolayer and chitosan/pectin alternating multilayer were bound onto the functionalized surfaces. Surface characteristics were systematically investigated using several probe techniques. In vitro bacterial adhesion and biofilm formation assays indicated that a single chitosan layer was incapable of hindering the adhesion of a Staphylococcus aureus bacterial strain, while up to 30% reduction was achieved by the chitosan/pectin layered assembly. On the other hand, chitosan and chitosan/pectin multilayer could retard Escherichia coli adhesion by 50% and 20%, respectively. Furthermore, plasma treated and graft copolymerized samples were also found effective to diminish the degree of adherence of Escherichia coli. http://www.mdpi.com/1420-3049/15/2/1007/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 1007 1027 1420-3049 Polysaccharides Coatings on Medical-Grade PVC: A Probe into Surface Characteristics and the Extent of Bacterial Adhesion 2010-02-23 doi: 10.3390/molecules15021007 Ahmad Asadinezhad Igor Novák Marián Lehocký František Bílek Alenka Vesel Ita Junkar Petr Sáha Anton Popelka http://www.mdpi.com/1420-3049/15/2/997/ The title compounds, (4-trifluoromethoxyphenyl)-2,5-dimethyl-3-(2-R-thiazol-4-yl)-1H-pyrroles, were prepared in four steps starting from commercially available 4-trifluoromethoxyaniline. The pyrrole (second ring) was added in one step using the Paal-Knorr method. The thiazole (third ring) was added in three steps using chloroacylation with chloroacetonitrile followed by heterocyclization with thioamides/thioureas. http://www.mdpi.com/1420-3049/15/2/997/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 997 1006 1420-3049 Synthesis of 1-(4-Trifluoromethoxyphenyl)-2,5-dimethyl-3-(2-R-thiazol-4-yl)-1H-pyrroles via Chain Heterocyclization 2010-02-23 doi: 10.3390/molecules15020997 Mykhaylo V. Vovk Oleksandr M. Pinchuk Andrij O. Tolmachov Andrei A. Gakh http://www.mdpi.com/1420-3049/15/2/988/ Thiosemicarbazone analogs of papaveraldine and related compounds 1–6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1–5 displayed cytotoxicity toward all the tested cell lines, while compounds 2–5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4)-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 µg/mL, respectively. In addition, 2-benzoylpyridine thio-semicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development. http://www.mdpi.com/1420-3049/15/2/988/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Article 988 996 1420-3049 Synthesis, Cytotoxic and Antimalarial Activities of Benzoyl Thiosemicarbazone Analogs of Isoquinoline and Related Compounds 2010-02-23 doi: 10.3390/molecules15020988 Ratchanok Pingaew Supaluk Prachayasittikul Somsak Ruchirawat http://www.mdpi.com/1420-3049/15/2/959/ By-products derived from food processing are attractive source for their valuable bioactive components and color pigments. These by-products are useful for development as functional foods, nutraceuticals, food ingredients, additives, and also as cosmetic products. Lycopene is a bioactive red colored pigment naturally occurring in plants. Industrial by-products obtained from the plants are the good sources of lycopene. Interest in lycopene is increasing due to increasing evidence proving its preventive properties toward numerous diseases. In vitro, in vivo and ex vivo studies have demonstrated that lycopene-rich foods are inversely associated to diseases such as cancers, cardiovascular diseases, diabetes, and others. This paper also reviews the properties, absorption, transportation, and distribution of lycopene and its by-products in human body. The mechanism of action and interaction of lycopene with other bioactive compounds are also discussed, because these are the crucial features for beneficial role of lycopene. However, information on the effect of food processing on lycopene stability and availability was discussed for better understanding of its characteristics. http://www.mdpi.com/1420-3049/15/2/959/ Tue, 23 Feb 2010 00:00:00 CET Molecules 2010-02-23 15 2 Review 959 987 1420-3049 Revealing the Power of the Natural Red Pigment Lycopene 2010-02-23 doi: 10.3390/molecules15020959 Kin-Weng Kong Hock-Eng Khoo K. Nagendra Prasad Amin Ismail Chin-Ping Tan Nor Fadilah Rajab http://www.mdpi.com/1420-3049/15/2/917/ Organocatalytic asymmetric α-oxidation and amination reactions of carbonyl compounds are highly useful synthetic methodologies, especially in generating chiral building blocks that previously have not been easily accessible by traditional methods. The concept is relatively new and therefore the list of new catalysts, oxidizing and aminating reagents, as well as new substrates, are expanding at an amazing rate. The scope of this review includes new reactions and catalysts, mechanistic aspects and synthetic applications of α-oxidation, hydroxylation, aminoxylation, amination, hydrazination, hydroxyamination and related α-heteroatom functionalization of aldehydes, ketones and related active methylene compounds published during 2005–2009. http://www.mdpi.com/1420-3049/15/2/917/ Thu, 11 Feb 2010 00:00:00 CET Molecules 2010-02-11 15 2 Review 917 958 1420-3049 Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds 2010-02-11 doi: 10.3390/molecules15020917 Tirayut Vilaivan Worawan Bhanthumnavin http://www.mdpi.com/1420-3049/15/2/878/ Huntington’s disease (HD) is an inheritable autosomal-dominant disorder whose causal mechanisms remain unknown. Experimental models have begun to uncover these pathways, thus helping to understand the mechanisms implicated and allowing for the characterization of potential targets for new therapeutic strategies. 3-Nitropropionic acid is known to produce in animals behavioural, biochemical and morphologic changes similar to those occurring in HD. For this reason, this phenotypic model is gaining attention as a valuable tool to mimick this disorder and further developing new therapies. In this review, we will focus on the past and present research of this molecule, to finally bring a perspective on what will be next in this promising field of study. http://www.mdpi.com/1420-3049/15/2/878/ Wed, 10 Feb 2010 00:00:00 CET Molecules 2010-02-10 15 2 Review 878 916 1420-3049 3-Nitropropionic Acid as a Tool to Study the Mechanisms Involved in Huntington’s Disease: Past, Present and Future 2010-02-10 doi: 10.3390/molecules15020878 Isaac Túnez Inmaculada Tasset Verónica Pérez-De La Cruz Abel Santamaría http://www.mdpi.com/1420-3049/15/2/871/ A new 1,4-diazepine, callysponine (1), was isolated from a South China Sea Callyspongia sp. marine sponge, together with four known proline-based diketopiperazines: cyclo-(S-Pro-R-Leu) (2), cyclo-(S-Pro-R-Val) (3), cyclo-(S-Pro-R-Ala) (4), andcyclo-(S-Pro-R-Tyr) (5). The new structure was determined on the basis of NMR and MS analysis, and the absolute stereochemistry was defined by NOESY spectroscopy and optical rotation. The structures of the known compounds were identified by comparison of their spectroscopic data with those reported in the literature. Callysponine (1) did not inhibit the growth of HepG2 (hepatoma carcinoma cell), A549 (lung carcinoma cell), and HeLa (cervical cancer cell) cell lines. http://www.mdpi.com/1420-3049/15/2/871/ Wed, 10 Feb 2010 00:00:00 CET Molecules 2010-02-10 15 2 Article 871 877 1420-3049 A New 1,4-Diazepine from South China Sea Marine Sponge Callyspongia Species 2010-02-10 doi: 10.3390/molecules15020871 Ri-Ming Huang Wei Ma Jun-De Dong Xue-Feng Zhou Tunhai Xu Kyung Jin Lee Xianwen Yang Shi-Hai Xu Yonghong Liu http://www.mdpi.com/1420-3049/15/2/857/ P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp. http://www.mdpi.com/1420-3049/15/2/857/ Tue, 09 Feb 2010 00:00:00 CET Molecules 2010-02-09 15 2 Article 857 870 1420-3049 Quercetin as a Potential Modulator of P-Glycoprotein Expression and Function in Cells of Human Pancreatic Carcinoma Line Resistant to Daunorubicin 2010-02-09 doi: 10.3390/molecules15020857 Sylwia Borska Miroslaw Sopel Magdalena Chmielewska Maciej Zabel Piotr Dziegiel http://www.mdpi.com/1420-3049/15/2/842/ Oligo(ε-caprolactone) and oligolactide were synthesized via ring-opening polymerization of cyclic esters in the presence of creatinine as initiators. Thus obtained oligomers were successfully used in the synthesis of novel polyurethane conjugates of norfloxacin. The structures of the polymers and conjugates were elucidated by means of MALDI-TOF MS, NMR and IR studies. http://www.mdpi.com/1420-3049/15/2/842/ Fri, 05 Feb 2010 00:00:00 CET Molecules 2010-02-05 15 2 Article 842 856 1420-3049 Seeking Polymeric Prodrugs of Norfloxacin. Part 2. Synthesis and Structural Analysis of Polyurethane Conjugates 2010-02-05 doi: 10.3390/molecules15020842 Marcin Sobczak Katarzyna Nurzyńska Waclaw Kolodziejski http://www.mdpi.com/1420-3049/15/2/834/ A new scalarane sesterterpene, phyllofolactone M (1), and a new sterol, (24E)-5α,6α-epoxystigmasta-7,24(28)-dien-3β-ol (3), together with a known sesterterpene, phyllofolactone B (2), were isolated from the South China Sea sponge Phyllospongia foliascens. Their structures were elucidated by spectroscopic analysis and comparison with known compounds. In addition, previous NMR data assignments for the known sesterterpene phyllofolactone B (2) were revised. http://www.mdpi.com/1420-3049/15/2/834/ Fri, 05 Feb 2010 00:00:00 CET Molecules 2010-02-05 15 2 Article 834 841 1420-3049 Sesterterpenes and a New Sterol from the Marine Sponge Phyllospongia foliascens 2010-02-05 doi: 10.3390/molecules15020834 Hong-Jun Zhang Yang-Hua Yi Fan Yang Wan-Sheng Chen Hou-Wen Lin http://www.mdpi.com/1420-3049/15/2/824/ Ceramides play a crucial role in the barrier function of the skin as well as in transmembrane signaling. In this study long aliphatic chain tartaric acid diamides able to replace ceramides in an in vitro model of the stratum corneum lipid matrix due to their similar physico-chemical properties were synthesized from diacetoxysuccinic anhydride in four steps. Their pro-apoptotic effect on fibroblast cells was also investigated. http://www.mdpi.com/1420-3049/15/2/824/ Fri, 05 Feb 2010 00:00:00 CET Molecules 2010-02-05 15 2 Article 824 833 1420-3049 Synthesis and Characterization of Long-Chain Tartaric Acid Diamides as Novel Ceramide-Like Compounds 2010-02-05 doi: 10.3390/molecules15020824 Bálint Sinkó Melinda Pálfi Szabolcs Béni József Kökösi Krisztina Takács-Novák http://www.mdpi.com/1420-3049/15/2/813/ A sustainable Knoevenagel condensation of a series of aldehydes with malononitrile and ethyl cyanoacetate is described. The process is based on the combination of microwave activation and hydroxyapatite catalysis under solvent-free conditions. Products are obtained in and high yields after short reaction times. The effects of the specific surface of porous calcium hydroxyapatite and microwave activation are discussed. http://www.mdpi.com/1420-3049/15/2/813/ Thu, 04 Feb 2010 00:00:00 CET Molecules 2010-02-04 15 2 Article 813 823 1420-3049 Microwave-Assisted and Efficient Solvent-free Knoevenagel Condensation. A Sustainable Protocol Using Porous Calcium Hydroxyapatite as Catalyst 2010-02-04 doi: 10.3390/molecules15020813 Siham Mallouk Khalid Bougrin Abdelaziz Laghzizil Rachid Benhida http://www.mdpi.com/1420-3049/15/2/804/ Ancient Chinese herbal texts as far back as the 4th Century Zhou hou bei ji fang describe methods for the use of Qing Hao (Artemisia annua) for the treatment of intermittent fevers. Today, the A. annua constituent artemisinin is an important antimalarial drug and the herb itself is being grown and used locally for malaria treatment although this practice is controversial. Here we show that the ancient Chinese methods that involved either soaking, (followed by wringing) or pounding, (followed by squeezing) the fresh herb are more effective in producing artemisinin-rich extracts than the usual current method of preparing herbal teas from the dried herb. The concentrations of artemisinin in the extracts was up to 20-fold higher than that in a herbal tea prepared from the dried herb, but the amount of total artemisinin extracted by the Chinese methods was much less than that removed in the herbal tea. While both extracts exhibited potent in vitro activities against Plasmodium falciparum, only the pounded juice contained sufficient artemisinin to suppress parasitaemia in P. berghei infected mice. The implications of these results are discussed in the context of malaria treatment using A. annua infusions. http://www.mdpi.com/1420-3049/15/2/804/ Thu, 04 Feb 2010 00:00:00 CET Molecules 2010-02-04 15 2 Article 804 812 1420-3049 Ancient Chinese Methods Are Remarkably Effective for the Preparation of Artemisinin-Rich Extracts of Qing Hao with Potent Antimalarial Activity 2010-02-04 doi: 10.3390/molecules15020804 Colin W. Wright Peter A. Linley Reto Brun Sergio Wittlin Elisabeth Hsu http://www.mdpi.com/1420-3049/15/2/793/ We report on the solubility of hen lysozyme (HEWL) in aqueous ethylammonium nitrate (EAN) as a function of water content. We find the solubility behavior to be complex, exhibiting both a maximum (400 mg/mL) at very high EAN content) and a minimum at intermediate EAN content. We exploit this solubility profile in a novel approach to generating crystals of hydrophilic proteins, based on rehydration of a high concentration protein solution. We describe the production of crystals of X-ray diffraction quality. Two related ionic liquid solvent systems, with the same solubility profiles but different effective pH characteristics, are identified for future evaluation. http://www.mdpi.com/1420-3049/15/2/793/ Thu, 04 Feb 2010 00:00:00 CET Molecules 2010-02-04 15 2 Communication 793 803 1420-3049 The Solubility of Hen Lysozyme in Ethylammonium Nitrate/H2O Mixtures and a Novel Approach to Protein Crystallization 2010-02-04 doi: 10.3390/molecules15020793 Nolene Byrne C. Austen Angell http://www.mdpi.com/1420-3049/15/2/780/ Pseudomonas aeruginosa is an opportunistic pathogen which is responsible for a wide range of infections. Production of virulence factors and biofilm formation by P. aeruginosa are partly regulated by cell-to-cell communication quorum-sensing systems. Identification of quorum-quenching reagents which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea epigallocatechin gallate (EGCG), which both function as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (ENR) from the bacterial type II fatty acid synthesis pathway. Our studies suggest that EGCG has a higher binding affinity towards ENR of P. aeruginosa and is an efficient quorum-quenching reagent. EGCG treatment was further shown to be able to attenuate the production of virulence factors and biofilm formation of P. aeruginosa. http://www.mdpi.com/1420-3049/15/2/780/ Wed, 03 Feb 2010 00:00:00 CET Molecules 2010-02-03 15 2 Article 780 792 1420-3049 Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents 2010-02-03 doi: 10.3390/molecules15020780 Liang Yang Yang Liu Claus Sternberg Søren Molin http://www.mdpi.com/1420-3049/15/2/766/ Some 3-(Substituted methylthio)-4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole derivatives were synthesized in six steps starting from easily accessible gallic acid. The resulting sulfides were then catalytically oxidized to the title sulfones with H2O2. The products were obtained in high yield under mild conditions and practically devoid of any by-products. The structures were confirmed by elemental analysis, IR, 1H- and 13C-NMR spectral data. Furthermore, a detailed X-ray crystallography structural analysis of model triazole 7g was carried out. http://www.mdpi.com/1420-3049/15/2/766/ Wed, 03 Feb 2010 00:00:00 CET Molecules 2010-02-03 15 2 Article 766 779 1420-3049 Synthesis and Crystal Structure of Novel Sulfone Derivatives Containing 1,2,4-Triazole Moieties 2010-02-03 doi: 10.3390/molecules15020766 Weiming Xu Baoan Song Pinaki Bhadury Yang Song Deyu Hu http://www.mdpi.com/1420-3049/15/2/747/ The CeO2 nanorods (CeNR) promote the oxidation of ethylbenzene (PhEt) and cyclohexene with t-BuOOH, at temperatures as low as 55 ºC. For both substrates the saturated C-H bonds are preferentially activated over the unsaturated ones. The catalyst seems fairly stable towards leaching phenomena. The liquid-phase oxidation catalysis may be associated with the Ce3+/Ce4+ inter-conversion in the one-electron redox processes mediating the formation of tert-butyl-(per)oxy radicals. CeNR is very effective in H2O2 disproportionation. Pre-treatment of CeNR with H2O2 or t-BuOOH prior to the catalytic reaction enhances the reaction rate of PhEt with t-BuOOH in comparison to CeNR. Textural characterization and spectroscopic studies suggest that catalytic activation is associated to defect sites. http://www.mdpi.com/1420-3049/15/2/747/ Tue, 02 Feb 2010 00:00:00 CET Molecules 2010-02-02 15 2 Article 747 765 1420-3049 Catalytic Performance of Ceria Nanorods in Liquid-Phase Oxidations of Hydrocarbons with tert-Butyl Hydroperoxide 2010-02-02 doi: 10.3390/molecules15020747 Andreia G. Macedo Sílvia E. M. Fernandes Anabela A. Valente Rute. A. S. Ferreira Luís D. Carlos João Rocha http://www.mdpi.com/1420-3049/15/2/735/ The chemical composition of the essential oils of Salvia africana L., Salvia elegans Vahl, Salvia greggii A. Gray, Salvia mellifera Green and Salvia munzii Epling, cultivated in Eboli (Salerno, Southern Italy), was studied by means of GC and GC-MS analyses. In all, 88 compounds were identified, 54 for S. africana, accounting for 95.4% of the total oil, 55 for S. elegans (92.9%), 50 for S. greggii (96.9%), 54 for S. mellifera (90.4%) and 47 for S. munzii (97.5%), respectively. In S. africana,the amount of monoterpenoids and sesquiterpenoids is very similar. For other species, the monoterpenoid percentage is greater than the amount of sesquiterpenoids. The oils of S. elegans, S. greggii and S. munzii were active inhibitors of germination and radical elongation of Raphanus sativus L. and Lepidium sativum L. http://www.mdpi.com/1420-3049/15/2/735/ Mon, 01 Feb 2010 00:00:00 CET Molecules 2010-02-01 15 2 Article 735 746 1420-3049 Chemical Composition and Antigerminative Activity of the Essential Oils from Five Salvia Species 2010-02-01 doi: 10.3390/molecules15020735 Laura De Martino Graziana Roscigno Emilia Mancini Enrica De Falco Vincenzo De Feo http://www.mdpi.com/1420-3049/15/2/709/ Conscious of the importance that stereochemical issues may have on the design of efficient organocatalyts for both Morita-Baylis-Hillman and aza-Morita-Baylis-Hillman reaction we have analyzed them in this minireview. The so-called standard reactions involve “naked” enolates which therefore should lead to the syn adducts as the major products, irrespective of the E, Z stereochemistry of the enolate. Accordingly, provided the second step is rate determining step, the design of successful bifunctional or polyfunctional catalysts has to consider the geometrical requirements imposed by the transition structures of the second step of these reactions. On the other hand, MBH and aza-MBH reactions co-catalyzed by (S)-proline and a secondary or tertiary amine (co-catalyst) involve the aldol-type condensation of either a 3-amino-substituted enamine, dienamine, or both, depending on the cases. A Zimmerman-Traxler mechanism defines the stereochemical issues regarding these co-catalyzed condensations which parallel those of the well established (S)-proline catalyzed aldol-like reactions. http://www.mdpi.com/1420-3049/15/2/709/ Mon, 01 Feb 2010 00:00:00 CET Molecules 2010-02-01 15 2 Review 709 734 1420-3049 Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions: Stereochemical Issues 2010-02-01 doi: 10.3390/molecules15020709 Javier Mansilla José M. Saá http://www.mdpi.com/1420-3049/15/2/699/ Using methanesulfonic acid as a catalyst, a series of cyclododeceno[b]indene derivatives were synthesized by the cyclization of α-benzylcyclododecanones, which were prepared by the reactions of cyclododecanones with a variety of substituted benzyl chlorides or bromides using NaH as a base. Their structures were confirmed by mp, IR spectra, 1H-NMR, 13C-NMR, MS, and x-ray diffraction. The preferred conformations were analyzed by crystal structure, 1H-NMR and quantum chemistry calculations, and compared with the x-ray diffraction structure of 2,3,5,6-bis(ortho-1,10-decylidene)dihydropyrazine. The results showed that the cyclododecene moiety adopted a preferred [1ene2333] conformation, and the substituted groups at aromatic ring had no significant influence on the conformation. http://www.mdpi.com/1420-3049/15/2/699/ Mon, 01 Feb 2010 00:00:00 CET Molecules 2010-02-01 15 2 Article 699 708 1420-3049 Facile Synthesis and Preferred Conformation Analysis of Cyclododeceno[b]indene 2010-02-01 doi: 10.3390/molecules15020699 Chunyan Zhang Shengyan Gong Li Zhang Daoquan Wang Mingan Wang http://www.mdpi.com/1420-3049/15/2/689/ The barks of two endemic Commiphora species namely, Commiphora ornifolia (Balf.f.) Gillett and Commiphora parvifolia Engl., were collected from Soqotra Island in Yemen and their essential oils were obtained by hydrodistillation. The chemical composition of both oils was investigated by GC and GC-MS. Moreover, the essential oils were evaluated for their antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria and one yeast species by using a broth micro-dilution assay for minimum inhibitory concentrations (MIC) and for their antioxidant activity by measuring the DPPH radical scavenging activity. A total of 45 constituents of C. ornifolia (85.6%) and 44 constituents of C. parvifolia (87.1%) were identified. The oil of C. ornifolia was characterized by a high content of oxygenated monoterpenes (56.3%), of which camphor (27.3%), α-fenchol (15.5%), fenchone (4.4%) and borneol (2.9%) were identified as the main components. High contents of oxygenated sesquiterpenes (36.1%) and aliphatic acids (22.8%) were found in C. parvifolia oil, in which caryophyllene oxide (14.2%), β-eudesmol (7.7%), bulnesol (5.7%), T-cadinol (3.7%) and hexadecanoic acid (18.4%) predominated. The results of the antimicrobial assay showed that both oils exhibited moderate to high antibacterial activity especially against Gram-positive bacteria. C. ornifolia oil was the most active. In addition, the DPPH-radical scavenging assay exhibited only weak antioxidant activities for both oils at the high concentration tested. http://www.mdpi.com/1420-3049/15/2/689/ Mon, 01 Feb 2010 00:00:00 CET Molecules 2010-02-01 15 2 Article 689 698 1420-3049 Chemical Analysis and Biological Activity of the Essential Oils of Two Endemic Soqotri Commiphora Species 2010-02-01 doi: 10.3390/molecules15020689 Ramzi A. Mothana Adnan J. Al-Rehaily Wulf Schultze http://www.mdpi.com/1420-3049/15/2/680/ Harvested longan (Dimocarpus longan Lour.) fruit are susceptible to decay caused by both bacterial and fungal infections. Ochratoxin A (OTA) is a kind of mycotoxin produced by a number of fungi. In this study, OTA was extracted from longan fruit pulp by 80% methanol and then loaded on C-18 solid-phase extraction columns. The extract solution was then analyzed by high-performance liquid chromatography - fluorescence detection (HPLC-FD) and an electron spray ionization-mass spectrometry (ESI-MS), respectively. The HPLC-FD analysis showed that a compound similar to OTA might exist in longan fruit pulp, but further analysis by the ESI-MS method demonstrated that OTA was not present in the longan pulp, indicating that the presence of OTA in longan fruit pulp detected by the HPLC-FD analysis needed to be confirmed by the ESI-MS method. http://www.mdpi.com/1420-3049/15/2/680/ Fri, 29 Jan 2010 00:00:00 CET Molecules 2010-01-29 15 2 Article 680 688 1420-3049 A Comparative Identification of Ochratoxin A in Longan Fruit Pulp by High Performance Liquid Chromatography-Fluorescence Detection and Electron Spray Ionization-Mass Spectrometry 2010-01-29 doi: 10.3390/molecules15020680 Jing Li Haihui Xie Bao Yang Xinhong Dong Linyan Feng Feng Chen Yueming Jiang http://www.mdpi.com/1420-3049/15/2/672/ A new flavone C-glycoside, isovitexin 6″-O-E-p-coumarate (1) and two known flavonoid glycosides—quercetin 3-O-β-D-glucuronopyranoside (2) and isoorientin (3)—were isolated from an ethanol extract of aerial parts of Clematis rehderiana. Their structures were determined by spectroscopic methods. The antioxidant effects of the two flavone C-glycosides were evaluated by both the MTT and DPPH assays. Compound 1 showed potent activities against H2O2-induced impairment in PC12 cells within the concentration range tested, whereas compound 3 scavenged DPPH radical strongly, with an IC50 value of 13.5 μM. http://www.mdpi.com/1420-3049/15/2/672/ Fri, 29 Jan 2010 00:00:00 CET Molecules 2010-01-29 15 2 Communication 672 679 1420-3049 A New Flavone C-Glycoside from Clematis rehderiana 2010-01-29 doi: 10.3390/molecules15020672 Zhi-Zhi Du Xian-Wen Yang Hao Han Xiang-Hai Cai Xiao-Dong Luo http://www.mdpi.com/1420-3049/15/2/660/ A series of eighteen azomethines has been synthesized by the reaction of appropriate primary aromatic amines with aryl and/or heteroaryl carboxaldehydes. The synthesized azomethines have been evaluated for their in vitro antileishmanial, antibacterial and antifungal activities. The results revealed some antifungal activity of most of the synthesized compounds, whereas the antileishmaniasis activity results highlighted that all synthesized azomethines inhibited parasite growth and most of them showed highly potent action towards Leishmania major promastigotes. No remarkable bactericidal activities were observed. http://www.mdpi.com/1420-3049/15/2/660/ Thu, 28 Jan 2010 00:00:00 CET Molecules 2010-01-28 15 2 Article 660 671 1420-3049 Antileishmanial, Antimicrobial and Antifungal Activities of Some New Aryl Azomethines 2010-01-28 doi: 10.3390/molecules15020660 Yasser M.S.A. Al-Kahraman Hassan. M.F. Madkour Dildar Ali Masoom Yasinzai http://www.mdpi.com/1420-3049/15/2/649/ An efficient and stereoselective catalytic system for the Heck cross coupling reaction using novel 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts (1, LHX) and Pd(OAc)2 loading has been reported. The palladium complexes derived from the salts 1a-f prepared in situ exhibit good catalytic activity in the Heck coupling reaction of aryl bromides under mild conditions. http://www.mdpi.com/1420-3049/15/2/649/ Thu, 28 Jan 2010 00:00:00 CET Molecules 2010-01-28 15 2 Article 649 659 1420-3049 Palladium-Catalyzed Heck Coupling Reaction of Aryl Bromides in Aqueous Media Using Tetrahydropyrimidinium Salts as Carbene Ligands 2010-01-28 doi: 10.3390/molecules15020649 Sedat Yaşar Emine Özge Özcan Nevin Gürbüz Bekir Çetinkaya İsmail Özdemir http://www.mdpi.com/1420-3049/15/2/639/ From the twigs of Miliusa mollis Pierre, three new compounds including (2S,3S)-2,3-dihydro-2-(4-methoxyphenyl)-3-methyl-5-[1(E)-propenyl]benzofuran, (7S,8S)- threo-Δ8'-4-methoxyneolignan and tyrosol-1-O-β-xylopyranosyl-(1→6)-O-β-gluco-pyranoside were isolated, along with seven known compounds. Their structures were elucidated through analysis of their spectroscopic data. http://www.mdpi.com/1420-3049/15/2/639/ Thu, 28 Jan 2010 00:00:00 CET Molecules 2010-01-28 15 2 Article 639 648 1420-3049 New Neolignans and a Phenylpropanoid Glycoside from Twigs of Miliusa mollis 2010-01-28 doi: 10.3390/molecules15020639 Kanokporn Sawasdee Tanawat Chaowasku Kittisak Likhitwitayawuid http://www.mdpi.com/1420-3049/15/2/627/ The essential oil of the stems and fruits of Caralluma europaea (Guss.) N.E.Br. (Apocynaceae) from Lampedusa Island has been obtained by hydrodistillation and its composition analyzed. The analyses allowed the identification and quantification of 74 volatile compounds, of which 16 were aromatic and 58 non-aromatic. Stems and fruits contained 1.4% and 2.7% of aromatic compounds respectively, while non-aromatic were 88.3% and 88.8%. Non-aromatic hydrocarbons were the most abundant compounds in both organs, followed by fatty acids. Data showed differences in the profiles between stems and fruits which shared only eighteen compounds; stems accounted for 38 compounds while fruits for 53. Fruits showed a higher diversity especially in aromatic compounds with twelve versus four in stems. Among the volatiles identified in stems and fruits of C. europaea 26 are present in other taxa of Apocynaceae, 52 are semiochemicals for many insects, and 21 have antimicrobial activity. The possible ecological role of the volatiles found is briefly discussed. http://www.mdpi.com/1420-3049/15/2/627/ Wed, 27 Jan 2010 00:00:00 CET Molecules 2010-01-27 15 2 Article 627 638 1420-3049 Essential Oil Composition of Stems and Fruits of Caralluma europaea N.E.Br. (Apocynaceae) 2010-01-27 doi: 10.3390/molecules15020627 Pietro Zito Maurizio Sajeva Maurizio Bruno Antonella Maggio Sergio Rosselli Carmen Formisano Felice Senatore http://www.mdpi.com/1420-3049/15/2/619/ In this paper we describe an isothermal rolling-circle amplification (RCA) protocol to detect gene point mutations on chips. The method is based on an allele-specific oligonucleotide circularization mediated by a special DNA ligase. The probe is circularized when perfect complementary sequences between the probe oligonucleotide and HIV cDNA gene. Mismatches around the ligation site can prevent probe circularization. The circularized probe (C-probe) can be amplified by rolling circle amplification to generate multimeric singlestranded DNA (ssDNA) under isothermal conditions. There are four sequence regions to bind respectively with fluorescent probe, RCA primer, solid probe and HIV cDNA template in the C-probe which we designed. These ssDNA products are hybridized with fluorescent probes and solid probes which are immobilized on a glass slide composing a regular microarray pattern. The fluorescence signals can be monitored by a scanner in the presence of HIV cDNA templates, whereas the probes cannot be circularized and signal of fluorescence cannot be found. The RCA array has capability of high-throughput detection of the point mutation and the single-nucleotide polymorphism (SNP).The development of C-probe-based technologies offers a promising prospect for situ detection, microarray, molecular diagnosis, single nucleotide polymorphism, and whole genome amplification. http://www.mdpi.com/1420-3049/15/2/619/ Wed, 27 Jan 2010 00:00:00 CET Molecules 2010-01-27 15 2 Article 619 626 1420-3049 Detection of HIV cDNA Point Mutations with Rolling-Circle Amplification Arrays 2010-01-27 doi: 10.3390/molecules15020619 Lingwei Wu Quanjun Liu Zhongwei Wu Zuhong Lu http://www.mdpi.com/1420-3049/15/2/613/ Besides two known glycosides, a new furostanol glycoside was isolated from the Fruits of Tribulus terrestris L. The structure of the new furostanol glycoside was established as 26-O-β-D-glucopyranosyl-(25S)-5α-furostane-20(22)-en-12-one-3β, 26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside (1) on the basis of 1D and 2D-NMR techniques, including COSY, HMBC, and HMQC correlations. http://www.mdpi.com/1420-3049/15/2/613/ Wed, 27 Jan 2010 00:00:00 CET Molecules 2010-01-27 15 2 Communication 613 618 1420-3049 A New Furostanol Glycoside from Tribulus terrestris 2010-01-27 doi: 10.3390/molecules15020613 Yajuan Xu Yonghong Liu Tunhai Xu Shengxu Xie Yunshan Si Yue Liu Haiou Zhou Tonghua Liu Dongming Xu http://www.mdpi.com/1420-3049/15/2/606/ Chemical investigation of the EtOH extract of the twigs of Calophyllum inophyllum collected in Hainan Province of China resulted in the isolation of two new prenylated xanthones, caloxanthone O (1) and caloxanthone P (2). Their structures were elucidated by a study of their physical and spectral data. Compound 1 exhibited cytotoxicity against human gastric cancer cell line (SGC-7901),with an IC50 value of 22.4 μg mL-1. http://www.mdpi.com/1420-3049/15/2/606/ Wed, 27 Jan 2010 00:00:00 CET Molecules 2010-01-27 15 2 Article 606 612 1420-3049 Caloxanthones O and P: Two New Prenylated Xanthones from Calophyllum inophyllum 2010-01-27 doi: 10.3390/molecules15020606 Hao-Fu Dai Yan-Bo Zeng Qi Xiao Zhuang Han You-Xing Zhao Wen-Li Mei http://www.mdpi.com/1420-3049/15/1/604/ The authors wish to make the following corrections to this paper [1]: http://www.mdpi.com/1420-3049/15/1/604/ Tue, 26 Jan 2010 00:00:00 CET Molecules 2010-01-26 15 1 Correction 604 605 1420-3049 Roy et al. On Two Novel Parameters for Validation of Predictive QSAR Models. Molecules, 2009, 14, 1660-1701 2010-01-26 doi: 10.3390/molecules15010604 Partha Pratim Roy Somnath Paul Indrani Mitra Kunal Roy http://www.mdpi.com/1420-3049/15/1/570/ Photoresponsive block copolymers (PRBCs) containing azobenzenes and other chromophores can be easily prepared by controlled polymerization. Their photoresponsive behaviors are generally based on photoisomerization, photocrosslinking, photoalignment and photoinduced cooperative motions. When the photoactive block forms mesogenic phases upon microphase separation of PRBCs, supramolecular cooperative motion in liquid-crystalline PRBCs enables them to self-organize into hierarchical structures with photoresponsive features. This offers novel opportunities to photocontrol microphase-separated nanostructures of well-defined PRBCs and extends their diverse applications in holograms, nanotemplates, photodeformed devices and microporous films. http://www.mdpi.com/1420-3049/15/1/570/ Tue, 26 Jan 2010 00:00:00 CET Molecules 2010-01-26 15 1 Review 570 603 1420-3049 Photoresponsive Block Copolymers Containing Azobenzenes and Other Chromophores 2010-01-26 doi: 10.3390/molecules15010570 Haifeng Yu Takaomi Kobayashi http://www.mdpi.com/1420-3049/15/1/554/ Three new enantiopure aryl-thioureas have been synthesized, N-(4-X-phenyl)-N-[1(S)-1-phenylethyl]thiourea, X= Cl, Br, and NO2 (compounds 1-3, respectively). Large single crystals of up to 0.5 cm3 were grown from methanol/ethanol solutions. Molecular structures were derived from X-ray diffraction studies and the crystal morphology was compared to calculations employing the Bravais-Friedel, Donnay-Harker model. Molecular packing was further studied with Hirshfeld surface calculations. Semi-empirical classical model calculations of refractive indices, optical rotation and the electro-optic effect were performed with OPTACT on the basis of experimentally determined refractive indices. Compound 3 (space group P 1 (No. 1)) was estimated to possess a large electro-optic coefficient r333 of approximately 30 pm/V, whereas 1 and 2 (space Group P 21 (No. 4) exhibit much smaller effects. http://www.mdpi.com/1420-3049/15/1/554/ Tue, 26 Jan 2010 00:00:00 CET Molecules 2010-01-26 15 1 Article 554 569 1420-3049 Structure, Morphology and Optical Properties of Chiral N-(4-X-phenyl)-N-[1(S)-1-phenylethyl]thiourea, X= Cl, Br, and NO2 2010-01-26 doi: 10.3390/molecules15010554 Werner Kaminsky Donald Responte Dan Daranciang Jose B. Gallegos Bao-Chau Ngoc Tran Tram-Anh Pham