Table of Contents

Abstract: The taxonomical relationship between Salvia pratensis and S. bertolonii has been unclear for a long time. Salvia bertolonii has alternatively been considered a synonym, a subspecies, a problematic subspecies and a form of Salvia pratensis. However, both these two species are sometimes used in traditional medicine instead of sage (Salvia officinalis) or as an adulteration for the same drug. In order to confirm the status of S. bertolonii, together with the potential identification characteristics for differentiation from sage, both taxa were analyzed through the analysis of their essential oils, together with the micromorphological characteristics of the leaf surface and the anatomy and morphology of the leaves. The obtained results show that there are clear differences in the quantity of essential oil (0.073% for S. pratensis and 0.0016% for S. berolonii). The major compound in the essential oil of S. pratensis was E-caryophyllene (26.4%) while in S. berolonii essential oil caryophyllene oxide was the major component (35.1%). The micromorphological differences are also pronounced in the leaf indumentum (density and distribution of certain types of non-glandular and glandular trichomes). Clear distinction between the investigated Salvia species is also observed in the leaf anatomy (in S. pratensis leaves are thinner, palisade tissue is made of 1-2 layers of cells, and leaves of S. bertolonii are characterized by 2-3 layers of palisade tissue cells, and consequently thicker).

Abstract: This study found that in Tris-HCl buffer, the resonance light scattering (RLS) intensity of the Eu³⁺-nicotinic acid system can be greatly enhanced by nucleic acids and the enhanced intensity is proportional to the concentration of nucleic acid in the range of 7×10^-8-1×10^-5 g∙mL^-1 for fsDNA, and its detection limit is 2×10^-8 g∙mL^-1. Based on this, a new method for the determination of nucleic acids is proposed. Synthetic and actual samples are determined satisfactorily. The interaction mechanism is also studied. It is thought that nucleic acid can bind with the Eu³⁺-nicotinic acid complex through electrostatic attraction and thus form a large Eu³⁺-nicotinic acid-nucleic acid complex.

Abstract: A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC₅₀ values of 9.0 and 18.8 μM against Plasmodia.

Abstract: From the ethyl acetate soluble fraction of a methanol/water extract of the herb Eupatorium perfoliatum L. (Asteraceae) six caffeic acid derivatives have been isolated and identified by 1D- and 2D-NMR spectroscopic data. Besides the common quinic acid derivatives 5-caffeoylquinic acid (chlorogenic acid), 3-caffeoylquinic acid (neochlorogenic acid) and 3,5-dicaffeoylquinic acid, three up to now unknown depsides of caffeic acid with glucaric acid have been isolated: 2,5-dicaffeoylglucaric acid, 3,4-dicaffeoylglucaric acid, and 2,4- or 3,5-dicaffeoylglucaric acid.

Abstract: In this study, the antioxidant activities of 15 flavonoids against lard oil oxidation were determined by using the Rancimat test. Quercetin, dihydromyricetin, luteolin and kaempferol showed the strongest antioxidant activity, with protection factor values (PF) of 11.50, 11.29, 4.24 and 2.49, respectively. The role of conjugated hydroxyl groups of the B and C ring is discussed. By using the following descriptors: ΔH_f (the difference in heat of formation between flavonoids and their free radicals resulted after hydrogen atom donation) and H_BC (the number of conjugated hydroxyl groups of the B and C ring), the result obtained in the antioxidant Rancimat test could be successfully explained.

Abstract: cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, ³¹P-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O₂ level in blood and affected the metabolism of phosphate compounds, while cisplatin had no such effects. When combined these two drugs showed synergistic effects, which matches the higher frequency of cardiotoxicity of the combination relative to the sole application of 5-FU. Preliminary results acquired on blood of patients receiving cisplatin/5-FU therapy verified observations obtained ex vivo. These results open a possibility of applying NMR in preclinical trials of new drugs in order to predict their ischemic potential.

Abstract: The reported structures of reaction products of enaminones with malononitrile in ethanolic piperidine are revised. A novel route to 2,3-dihydropyridazine-4-carboxylic acids 4a-c via reactions of 2-cyano-5-(dimethylamino)-5-arylpenta-2,4-dienamides 8a-c with nitrous acid or with benzenediazonium chloride is reported. Compounds 8a-c are converted to 1,2-dihydropyridine-3-carboxylic acid and 1,2-dihydropyridine-3-carbonitrile derivatives upon reflux in EtOH/ HCl and in AcOH.

Abstract: A simple route to 3-oxoalkanonitrile 5, aprecursor of the title compounds is described. Reaction of enaminones 2 with hydroxylamine hydrochloride in ethanol yielded aldoximes 3 that were converted readily into 5 in basic medium. This method has been successfully applied with a number of substrates and resulted in excellent yields of the products. Reacting 5 with trichloroacetonitrile afforded 3-amino-2-aroyl-4,4,4-trichloro-2-butenenitriles 6 that condensed with hydrazines to yield 3-amino-1H-pyrazole-4-carbonitrilederivatives 8. Substituted pyrazolo[1,5-a]pyridmidines have been prepared with regioselective condensation reactions of 8 with nonsymmetrical dielectrophiles. The structures of compounds obtained were deduced based on ¹H-NMR, ¹H-¹⁵N HMBC- measurements.

Abstract: The structure previously assigned to the phenolic noraporphine alkaloid, (-)-norannuradhapurine has been confirmed by a total synthesis of the racemic alkaloid in which the key step involved the formation of the C ring by a radical-initiated cyclization. although inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028, (±)-norannuradhapurine inhibits the production of NO, PGE₂, TNF-a, IL-1b and IL-6 and the expression of iNOS and COX-2 in RAW 264.7 macrophages stimulated with LPS in vitro.

Abstract: We previously isolated a novel natural product, designated kohamaic acid A (KA-A, compound 1), as an inhibitor of the first cleavage of fertilized sea urchin eggs, and found that this compound could selectively inhibit the activities of mammalian DNA polymerases (pols). In this paper, we investigated the structure and bioactivity of KA-A and its chemically synthesized 11 derivatives (i.e., compounds 2–12), including KA-A - fatty acid conjugates. The pol inhibitory activity of compound 11 [(1S*,4aS*,8aS*)-17-(1,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethyl-naphthalen-1-yl)heptadecanoic acid] was the strongest among the synthesized compounds, and the range of IC₅₀ values for mammalian pols was 3.22 to 8.76 µM; therefore, the length of the fatty acid side chain group of KA-A is important for pol inhibition. KA-A derivatives could prevent human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of mammalian pols. Since pol β is the smallest molecule, we used it to analyze the biochemical relationship with KA-A derivatives. From computer modeling analysis (i.e., docking simulation analysis), these compounds bound selectively to four amino acid residues (Leu11, Lys35, His51 and Thr79) of the N-terminal 8-kDa domain of pol β, and the binding energy between compound 11 and pol β was largest in the synthesized compounds. The relationship between the three-dimensional molecular structures of KA-A-related compounds and these inhibitory activities is discussed.

Abstract: Neem oil is obtained from the seeds of the tree Azadirachta indica. Its chemical composition is very complex, being rich in terpenoids and limonoids, as well as volatile sulphur modified compounds. This work focused on the evaluation of a component of the whole Neem oil obtained by methanolic extraction and defined as MEX. Cytotoxicity was assessed on two different cell populations: a stabilized murine fibroblast line (3T6) and a tumor cell line (HeLa). The data presented here suggest a differential sensitivity of these two populations, the tumor line exhibiting a significantly higher sensitivity to MEX. The data strongly suggest that its toxic target is the cell membrane. In addition the results presented here imply that MEX may contain one or more agents that could find a potential use in anti-proliferative therapy.

Abstract: Various cultivars of Perilla frutescens (L.) (var. crispa and var. frutescens) Britt. were harvested in China and Japan. They were easily differentiated on the basis of their foliage color, that varied from red to green. Water extracts of dried plants were investigated for their antioxidant activity (AA) and their polyphenolic compounds compared. Among them, cinnamic acid derivatives (coumaroyl tartaric acid, caffeic acid and rosmarinic acid), flavonoids (apigenin 7-O-caffeoylglucoside, scutellarein 7-O-diglucuronide, luteolin 7-O-diglucuronide, apigenin 7-O-diglucuronide, luteolin 7-O-glucuronide, and scutellarein 7-O-glucuronide) and anthocyanins (mainly cis-shisonin, shisonin, malonylshisonin and cyanidin 3-O-(E)-caffeoylglucoside-5-O-malonylglucoside) were quantified. AA assays are based on the inhibition of the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The DPPH radical scavenging activity was calculated as Trolox ^® [(±)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid] equivalent antioxidant capacity (TEAC). The mean amount of total phenolics of the water extracts (4-29 µmol/100 mL) and the TEAC value calculated (23-167 µmol TE/100 mL) confirmed the high antioxidant activity of these leaf water extracts. These results were highly correlated within some o-dihydroxylated polyphenolic compounds and AA.

Abstract: The purpose of this research was to investigate the relationship between selenium levels, thyroid function and other coronary risk factors in 140 Saudi subjects without overt coronary heart disease stratified by age. Demographic data and serum fasting lipid profile, glucose, thyroid function tests, selenium status and dietary intake was assessed. The relationships between selenium status, thyroid function and cardiovascular risk factors were assessed by univariate and multivariate analysis. The results showed that thyroid hormone levels did not differ with age. Erythrocyte glutathione peroxidase (GPx) levels were significantly higher in the youngest vs. oldest tertile (p<0.0001). Selenium and iodine intake did not differ significantly with age tertile, but the average intake for the population sample was below the estimated average requirements for both elements. Serum lipoprotein (a) concentrations correlated with selenium (r = 0.417, p<0.0001) and TSH (r = 0.172, p<0.05). After adjustment for confounding variables; serum fT₄ and erythrocytes GPx remained significant determinants of serum TSH levels, whilst serum selenium and TSH were determinants of serum fT₄ levels. Serum Lp(a), a coronary risk factor, was strongly related to measures of selenium status. A significant relationship between measures of selenium status and thyroid function was found. Serum Lp(a) a known risk factor for cardiovascular disease was also related to selenium status in our population.

Abstract: This investigation describes the synthesis and biological evaluation of a series of oxabicyclic analogues related to the helminthosporins. Four oxabicycles were prepared by [4+3] cycloaddition of an oxyallyl carbocation, generated in situ from 2,4-dibromopentan-3-one, with selected furans. Functional group manipulations of the oxabicyclic architecture generated nine further derivatives. The phytotoxic properties of these oxabicycles were evaluated as their ability to interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings. In both species, the most active compounds were oxabicycles possessing a carbonyl group conjugated with a double bond.

Abstract: Transition metal complexes of Co(II), Ni(II) and Cu(II) metal ions with general stoichiometry [M(L)X]X and [M(L)SO₄], where M = Co(II), Ni(II) and Cu(II), L = 3,3’-thiodipropionic acid bis(4-amino-5-ethylimino-2,3-dimethyl-1-phenyl-3-pyrazoline) and X = NO₃^-, Cl^- and OAc^-, have been synthesized and structurally characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements and spectral techniques like IR, UV and EPR. The nickel(II) complexes were found to have octahedral geometry, whereas cobalt(II) and copper(II) complexes were of tetragonal geometry. The covalency factor (β) and orbital reduction factor (k) suggest the covalent nature of the complexes. The ligand and its complexes have been screened for their antifungal and antibacterial activities against three fungi, i.e. Alternaria brassicae, Aspergillus niger and Fusarium oxysporum and two bacteria, i.e. Xanthomonas compestris and Pseudomonas aeruginosa.

Abstract: Seven pimarane type-diterpenes re-isolated from Viguiera arenaria Baker and two semi-synthetic pimarane derivatives were evaluated in vitro against the following main microorganisms responsible for dental caries: Streptococcus salivarius, S. sobrinus, S. mutans, S. mitis, S. sanguinis and Lactobacillus casei. The compounds ent-pimara-8(14),15-dien-19-oic acid (PA); ent-8(14),15-pimaradien-3b-ol; ent-15-pimarene-8b,19-diol; ent-8(14),15-pimaradien-3b-acetoxy and the sodium salt derivative of PA were the most active compounds, displaying MIC values ranging from 2 to 8 μg∙mL^-1. Thus, this class of compounds seems promising as a class of new effective anticariogenic agents. Furthermore, our results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new natural compounds that could be employed in the development of oral care products.

Abstract: Chocolate contains a wide range of antioxidants that includes soluble phenolic compounds (phenolic acids, catechin, epicatechin, and proanthocyanidins), insoluble polymeric phenolics and methylxanthines. The objective of this study was to determine phenolic and theobromine contents in dark (DC), milk (MC), and white (WC) chocolates commonly found in the Malaysian marketplace. Total phenolic and flavonoids were determined by means of a spectrometric assay, while catechin, epicatechin and theobromine were quantified using a reverse-phase HPLC method. Dark chocolates exhibited the highest phenolics and flavonoids contents, followed by milk and white chocolates. Catechin and epicatechin were major flavonoids detected in dark chocolates. Theobromine was detected in dark and milk chocolates, but not in white chocolates. A high correlation (r= 0.93) between total phenolic and flavonoid contents, indicating that the major phenolic compounds in dark chocolates belong to the flavonoid class. When nutrition and health promotion are of concern, dark chocolates would be recommended over milk and white chocolates owing to their higher contents of antioxidant phenolic compounds.

Abstract: Coumarins, as a family of molecules, exhibit a wide range of fluorescence emission properties. In many cases, this fluorescence is extremely sensitive to the local environment of the molecule, especially the local polarity and microviscosity. In addition, coumarins show a wide range of size, shape, and hydrophobicity. These properties make them especially useful as fluorescent probes of heterogeneous environments, such as supramolecular host cavities, micelles, polymers and solids. This article will review the use of coumarins to probe such heterogeneous systems using fluorescence spectroscopy.

Abstract: The potential antifungal effects of Thymus vulgaris L., Thymus tosevii L., Mentha spicata L., and Mentha piperita L. (Labiatae) essential oils and their components against 17 micromycetal food poisoning, plant, animal and human pathogens are presented. The essential oils were obtained by hydrodestillation of dried plant material. Their composition was determined by GC-MS. Identification of individual constituents was made by comparison with analytical standards, and by computer matching mass spectral data with those of the Wiley/NBS Library of Mass Spectra. MIC’s and MFC’s of the oils and their components were determined by dilution assays. Thymol (48.9%) and p-cymene (19.0%) were the main components of T. vulgaris, while carvacrol (12.8%), a-terpinyl acetate (12.3%), cis-myrtanol (11.2%) and thymol (10.4%) were dominant in T. tosevii. Both Thymus species showed very strong antifungal activities. In M. piperita oil menthol (37.4%), menthyl acetate (17.4%) and menthone (12.7%) were the main components, whereas those of M. spicata oil were carvone (69.5%) and menthone (21.9%). Mentha sp. showed strong antifungal activities, however lower than Thymus sp. The commercial fungicide, bifonazole, used as a control, had much lower antifungal activity than the oils and components investigated. It is concluded that essential oils of Thymus and Mentha species possess great antifungal potential and could be used as natural preservatives and fungicides.

Abstract: Some novel2,3-dioxo-5-(substituted)arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and ¹H-NMR spectra.

Abstract: The alcoholic extract from seed kernels of Thai mango (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloylglucopyranose) exhibited potent, dose-dependent inhibitory effects on tyrosinase with respect to L-DOPA. Molecular docking studies revealed that the binding orientations of the phenolic principles were in the tyrosinase binding pocket and their orientations were located in the hydrophobic binding pocket surrounding the binuclear copper active site. The results indicated a possible mechanism for their anti-tyrosinase activity which may involve an ability to chelate the copper atoms which are required for the catalytic activity of tyrosinase.

Abstract: Activity-guided fractionation of a MeOH extract of the roots of Saussurea lappa C.B.Clarke (Compositae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibition assay, led to the isolation of four active constituents: betulinic acid (1), betulinic acid methyl ester (2), mokko lactone (3) and dehydrocostuslactone (4), along with nine inactive compounds. Our findings indicate that betulinic acid (1) and its methyl ester 2, as well as the two guaiane sesquiterpenoids 3 and 4 are potential lead moieties for the development of new PTP1B inhibitors.

Abstract: The essential oils of the aerial parts of Ocimum basilicum Linn.var. pilosum (Willd.) Benth., an endemic medicinal plant growing in China, was obtained by hydrodistillation and analysed by GC-MS. Fifteen compounds, representing 74.19% of the total oil were identified. The main components were as follows: linalool (29.68%), (Z)-cinnamic acid methyl ester (21.49%), cyclohexene (4.41%), α- cadinol (3.99%), 2,4-diisopropenyl-1-methyl-1-vinylcyclohexane (2.27%), 3,5-pyridine-dicarboxylic acid, 2,6-dimethyl-diethyl ester (2.01%), β-cubebene (1.97%), guaia-1(10),11-diene (1.58%), cadinene (1.41%) (E)-cinnamic acid methyl ester (1.36%) and β-guaiene (1.30%). The essential oils showed significant antifungal activity against some plant pathogenic fungi.

Abstract: There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC₅₀ <0.5 mg/mL) while two others displayed IC₅₀ <1 mg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasisand for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.

Abstract: In this study, five biologically phenolic antioxidant Turkish red wines from different regions of Turkey were determined using HPLC with PDA detection. The antioxidant capacities (AC) of the investigated wines are also determined and the relationship between the phenol content and antioxidant capacity is discussed. The results show that Kalecik Karası, Merlot and Cabernet Sauvignon AC values ranged between 15.8-18.7 mmol/L, 15.8-17.6 mmol/L and 18.1-22.6 mmol/L, respectively. Generally, Cabernet Sauvignon wines not only had higher levels of phenolic antioxidants, such as catechin, epicatechin and gallic acid, but also higher antioxidant capacities compared to Kalecik Karası and Merlot wines. When the results were compared on the basis of geographical area, Aegean red wines were found to contain generally higher levels of biologically important phenolics and thus to have more antioxidant capacity compared to the wines of the other regions studied.

Abstract: Phenolic derivatives are among the most important contaminants present in the environment. These compounds are used in several industrial processes to manufacture chemicals such as pesticides, explosives, drugs and dyes. They also are used in the bleaching process of paper manufacturing. Apart from these sources, phenolic compounds have substantial applications in agriculture as herbicides, insecticides and fungicides. However, phenolic compounds are not only generated by human activity, but they are also formed naturally, e.g., during the decomposition of leaves or wood. As a result of these applications, they are found in soils and sediments and this often leads to wastewater and ground water contamination. Owing to their high toxicity and persistence in the environment, both, the US Environmental Protection Agency (EPA) and the European Union have included some of them in their lists of priority pollutants. Current standard methods of phenolic compounds analysis in water samples are based on liquid–liquid extraction (LLE) while Soxhlet extraction is the most used technique for isolating phenols from solid matrices. However, these techniques require extensive cleanup procedures that are time-intensive and involve expensive and hazardous organic solvents, which are undesirable for health and disposal reasons. In the last years, the use of news methodologies such as solid-phase extraction (SPE) and solid-phase microextraction (SPME) have increased for the extraction of phenolic compounds from liquid samples. In the case of solid samples, microwave assisted extraction (MAE) is demonstrated to be an efficient technique for the extraction of these compounds. In this work we review the developed methods in the extraction and determination of phenolic derivatives in different types of environmental matrices such as water, sediments and soils. Moreover, we present the new approach in the use of micellar media coupled with SPME process for the extraction of phenolic compounds. The advantages of micellar media over conventional extractants are reduction of organic solvent, low cost, easy handling and shorter time procedures.

Abstract: The antimicrobial activity of methanol and acetone extracts of Butomus umbellatus, Polygonum amphibium, and two species of the genus Sparganium (S. erectum and S. emersum)against three Gram-positive, five Gram-negative bacteria and one fungus was assessed by the disk diffusion method. The microorganisms used were Staphylococcus aureusATCC-29740, Escherichia coli ATCC-25922, Pseudomonas aeruginosa ATCC-15442, Salmonella typhi NCTC-9394, Klebsiella pneumoniae NCTC-5046, Proteus vulgaris ATCC-7829, Bacillus subtilis ATCC-6633, Corynebacterium diphteriae RSHM-633 and Candida albicans ATCC-10231. Methanol extracts of the plants did not exhibit any inhibitory activity against any of the microorganisms, while the acetone extracts of the all tested plants only showed significant activity against Bacillus subtilis, with inhibition zones and minimal inhibitory concentration values in the 7-16 mm and 0.49-12.50 mg/mL ranges, respectively.

Abstract: In recent years vitamin B6 has become a focus of research describing the compound’s critical function in cellular metabolism and stress response. For many years the sole function of vitamin B6 was considered to be that of an enzymatic cofactor. However, recently it became clear that it is also a potent antioxidant that effectively quenches reactive oxygen species and is thus of high importance for cellular well-being. In view of the recent findings, the current review takes a look back and summarizes the discovery of vitamin B6 and the elucidation of its structure and biosynthetic pathways. It provides a detailed overview on vitamin B6 both as a cofactor and a protective compound. Besides these general characteristics of the vitamin, the review also outlines the current literature on vitamin B6 derivatives and elaborates on recent findings that provide new insights into transport and catabolism of the compound and on its impact on human health.

Abstract: The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters to afford symmetrically- and dissymmetrically-disubstituted imidazole-4,5-dicarboxamides with intramolecularly hydrogen bonded conformations that predispose the presentation of amino acid pharmacophores. In this work, a total of 45 imidazole-4,5-dicarboxamides bearing amino acid esters were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by ¹H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap.

Abstract: Synthesis and characterization of resorcinol-acetone copolymer is described. The polymer was prepared by trifluoroacetic acid-catalyzed polymerization of resorcinol with acetone. According to the ¹H-NMR, ¹³C-NMR, and MALDI-TOF Mass spectra data, the obtained polymer had three types of repeating units: isopropylidene bridged-resorcinol, chromane ring, and spiro-shaped double chromane ring, indicating that polymerization proceeded via simultaneous addition-condensation and cyclization of resorcinol with acetone. The obtained polymer can be useful not only for the development of plastic materials such as thermosets, adhesives, and coatings but also for the synthesis of biomaterials such as antimicrobial agents, pesticides, and medicines.

Abstract: The synthetic access to 2-sec-amino-4H-3,1-benzothiazin-4-ones 2 was explored. Compounds 2 were available from methyl 2-thioureidobenzoates 1, 2-thioureidobenzoic acids 3, and novel 2-thioureidobenzamides 6, respectively, under different conditions. 2-Alkylthio-4H-3,1-benzothiazin-4-ones 5 have been prepared from anthranilic acid following a two step route. Both, benzothiazinones 2 and 5 underwent ring cleavage reactions to produce thioureas 1 and 6, respectively. Twelve benzothiazinones were evaluated as inhibitors against a panel of eight proteases and esterases to identify one selective inhibitor of human cathepsin L, 2b, and one selective inhibitor of human leukocyte elastase, 5i.

Abstract: A fast, general, environmentally friendly and facile method for preparation of five- and six-membered ring diazaheterocylic salts under microwave irradiation is presented. The N-alkylation reactions of imidazole, pyrimidine, pyridazine and phthalazine have been studied. The microwaves remarkably accelerated these N-alkylations, the reaction times decreased dramatically, the reaction conditions were milder, the consumed energy decreased considerably and the amount of solvents used was reduced substantially. Consequently, the microwave assisted alkylation of N-containing heterocycles could be considered eco-friendly. In some cases, under MW irradiation the yields are also higher. A comparative study of microwave vs. classical conditions (liquid solvents) has been done. Twelve new diazaheterocylic salts of potential practical interest were obtained.

Abstract: n/a

Abstract: A new atisane-type diterpene, ent-16α-hydroxy-atisane-3,4-lactone (4) and three known diterpenes, ent-16α-hydroxy-atisane-3-one (1), ent-atisane-3β,16α-diol (2), ent-3,4-seco-16α-hydroxyatis- 4(19)-en -3-oic acid (3) were isolated from the bark of the mangrove plant Excoecaria agallocha. Their structures and relative stereochemistry were elucidated by means of extensive NMR and MS analysis. Compound 3 exhibited significant anti-microfouling activity against the adherence of Pseudomonas pseudoalcaligenes, with an EC₅₀ value of 0.54 ± 0.01 ppm.

Abstract: Recent advances in molecular dynamics simulation methodologies and computational power have allowed accurate predictions of dendrimer size, shape, and interactions with bilayers and polyelectrolytes with modest computational effort. Atomistic and coarse-grained (CG) models show strong interactions of cationic dendrimers with lipid bilayers. The CG simulations with explicit lipid and water capture bilayer penetration and pore formation, showing that pore formation is enhanced at high dendrimer concentration, but suppressed at low temperature and high salt concentration, in agreement with experiments. Cationic linear polymers have also been simulated, but do not perforate membranes, evidently because by deforming into a pancake, the charges on a linear polymer achieve intimate contact with a single bilayer leaflet. The relatively rigid dendrimers, on the other hand, penetrate the bilayer, because only by interacting with both leaflets can they achieve a similar degree of contact between charged groups. Also, a “dendrimer-filled vesicle” structure for the dendrimer-membrane interaction is predicted by mesoscale thermodynamic simulations, in agreement with a picture derived from experimental observations. In simulations of complexes of dendrimer and polyelectrolyte, anionic linear chains wrap around the cationic dendrimer and penetrate inside it. Overall, these new results indicate that simulations can now provide predictions in excellent agreement with experimental observations, and provide atomic-scale insights into dendrimer structure and dynamics.

Abstract: Phenolic compounds may be of natural or anthropogenic origin and be present in the environment as well as in food. They comprise a large and diverse group of compounds that may be either beneficial or harmful for consumers. In this review first a non-exhausting overview of interesting phenolics is given, in particular with regards to their presence in environment and food. For some of these compounds, beneficial, toxicological and/or optionally endocrine disrupting activities will be presented. Further, immunochemical detection and/or isolation methods developed will be discussed, including advantages and disadvantages thereof in comparison with conventional analytical methods such as HPLC, GC, MS. A short overview of new sensor-like methods will also be included for present and future application.

Abstract: Solvent-free synthesis of pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones by ball-milling and without any catalyst is described. This method provides several advantages such as being environmentally friendly, using a simple workup procedure, and affording high yields.

Abstract: The aim of this paper was to assess the total antioxidant capacity of some commercial fruit juices (namely citrus), spectrophotometrically and by the biamperometric method, using the redox couple DPPH· (2,2-diphenyl-1-picrylhydrazyl)/DPPH (2,2-diphenyl-1-picrylhydrazine). Trolox^® was chosen as a standard antioxidant. In the case of the spectrophometric method, the absorbance decrease of the DPPH· solution was followed. For the biamperometric method, the influence of some parameters like the potential diference, ΔE, DPPH· concentration, and Trolox^® concentration was investigated. The calibration graph obtained for Trolox^® presents linearity between 5 and 30 µM, (y = 0.059 x + 0.0564, where y represents the value of current intensity, expressed as μA and x the value of Trolox^® concentration, expressed as μM; r² = 0.9944). The R.S.D. value for the biamperometric method was 1.29% (n = 10, c = 15 μM Trolox^®). In the case of the spectrophotometric method, the calibration graph obtained for Trolox^® presents linearity between 0.01 and 0.125 mM (y = -9.5789 x+1.4533, where y represents the value of absorbance and x, the value of Trolox^® concentration, expressed as mM; r² = 0.9963). The R.S.D. value for the spectrophotometric method was 2.05%. Both methods were applied to total antioxidant activity determination in real samples (natural juices and soft drinks) and the results were in good agreement.

Abstract: The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide(1), which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR)-based binding assays. Four compounds – 1, 2b, 2k and 2l –showed moderate FP-2 inhibition activity, with IC₅₀ values of 10.0-39.4 μM, and the inhibitory activityof compound 2k was ~3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity.

Abstract: Water infusions of Ligustrum delavayanum and Ligustrum vulgare leaves and eight phenolics isolated therefrom have been assayed in vitro on ofloxacin-induced genotoxicity in the unicellular flagellate Euglena gracilis. The tested compounds luteolin, quercetin, luteolin-7-glucoside, luteolin-7-rutinoside, quercetin-3-rutinoside, apigenin-7-rutinoside, tyrosol and esculetin inhibited the mutagenic activity of ofloxacin (43 µM) in E. gracilis. Water infusions from leaves of L. delavayanum and L. vulgare showed higher antimutagenic effect (p_t < 0.001). The activity of these samples against ofloxacin (86 µM)-induced genotoxicity was lower, but statistically significant (p_t < 0.05), excluding the water infusion of L. delavayanum leaves (p_t < 0.01). Efficacy of quercetin, luteolin-7-rutinoside, apigenin-7-rutinoside was insignificant. The antimutagenic effect of most phenolics we studied could be clearly ascribed to their DPPH scavenging activity, substitution patterns and lipophilicity.

Abstract: Five thiourea derivative ligands and their Ni²⁺ and Cu²⁺ complexes have been synthesized. The compounds were screened for their in vitro anti-bacterial activity using Gram-positive bacteria (two different standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus) and Gram-negative bacteria (Esherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus vulgaris, Enterobacter aerogenes) and in vitro anti-yeast activity (Candida albicans, Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis). The minimum inhibitory concentration was determined for all ligands and their complexes. In vitro anti-yeast activity of both ligands and their metal complexes is greater than their in vitro anti-bacterial activity. The effect of the structure of the investigated compounds on the antimicrobial activity is discussed.

Abstract: A solvent-free synthesis of 1,4-disubstituted-1,2,3-triazoles using neat azides and alkynes and a copper(I) polymer supported catalyst (Amberlyst^® A21•CuI) is presented herein. As it provides the products in high yields and purities within minutes, this method thus being characterized as a "flash" synthesis, and was exemplified through the synthesis of a 24-compound library on a small scale.

Abstract: Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models.

Abstract: Coniferyl ferulate, which is noted for its multiple pharmacological activities and chemical instability, is abundant in Angelica sinensis. In this paper, five methods, namely sonication extraction (SE), pressurized liquid extraction (PLE), supercritical fluid extraction (SFE), hydrodistillation (HD) and decoction (DC) for extraction of coniferyl ferulate, as well as ferulic acid, Z/E-ligustilide and Z/E-butylidenephthalide, from A. sinensis were optimized and compared. The results showed that the order of extraction efficiency was: PLE»SE>SFE>>HD, DC. The compositions of the SE, PLE and SFE extracts, which had a high ratio of coniferyl ferulate, were very similar, while no coniferyl ferulate was obtained by HD and DC, though they had high selectivity for the extraction of ligustilide and ferulic acid, respectively. It was noteworthy that the content of ligustilide and coniferyl ferulate was not detectable in the decoction, the commonly used oral administration form of Traditional Chinese Medicines in clinical practice.

Abstract: A new anthraquinone, Rubiacordone A (1) (6-acetoxy-1-hydroxy-2-methylanthraquinone-3-O-α-L-rhamnopyranoside), was isolated together with the known anthraquinone, 1-acetoxy-6-hydroxy-2-methylanthraquinone-3-O-[α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside] (2), from the dried roots of Rubia cordifolia. Their structures were elucidated on the basis of extensive 1D and 2D-NMR, as well as HRESI-MS spectroscopic analysis. Metabolites 1 and 2 showed considerable antimicrobial activity against Gram-positive bacteria.

Abstract: Bioactivity-guided fractionation led to the successful isolation of antiosteoporotic components, i.e. physicion (1), rubiadin-1-methyl ether (2), 2-hydroxy-1-methoxy- anthraquinone (3), 1,2-dihydroxy-3-methylanthraquinone (4), 1,3,8-trihydroxy-2-methoxy- anthraquinone (5), 2-hydroxymethyl-3-hydroxyanthraquinone (6), 2-methoxyanthraquinone (7) and scopoletin (8) from an ethanolic extract of the roots of Morinda officinalis. Compounds 4-8 are isolated for the first time from M. officinalis. Among them, compounds 2 and 3 promoted osteoblast proliferation, while compounds 4, 5 increased osteoblast ALP activity. All of the isolated compounds inhibited osteoclast TRAP activity and bone resorption, and the inhibitory effects on osteoclastic bone resorption of compounds 1 and 5 were stronger than that of other compounds. Taken together, antiosteoporotic activity of M. officinalis and its anthraquinones suggest therapeutic potential against osteoporosis.

Abstract: As has now become a custom for Molecules, as one year ends and another starts its Publisher and Editor-in-Chief would like to take stock of our progress in 2008 and offer our readership a preview of things to come in 2009. Just as we had hoped in last year’s editorial [1], the year that just concluded proved to be another outstanding one for MDPI's flagship journal Molecules. By year’s end we had published 239 papers and three Editorials or Editor's Notes for a total of 3,252 pages. While the 8% growth in the number of papers published compared to 2007 may appear modest, the number of pages published represented a 22% increase over the prior year, and was largely attributable to the increase in the number of reviews published. [...]