Molecules, Volume 14, Issue 5 (May 2009) – 28 articles , Pages 1652-1965

From the leaves of Duranta repens (Verbenaceae) two new triterpene saponins, named durantanin IV (1) and V (2)were isolated.In addition, ten known compounds were isolated, namely a bidesmosidic saponin, oleanolic acid, three phenylethanoids and five flavonoids. All metabolites were isolated for the first time from this genus except for 3 (oleanolic acid) and 7 (E/Z acteoside). The structures were determined mainly by spectroscopic methods (UV, IR, HRESI-MS, ¹H-, ¹³C-NMR, ¹H-¹H COSY, HSQC and HMBC). Cytotoxic screening of the chloroform, ethyl acetate and methanol extracts was carried out on brine shrimps. In addition, the investigated methanol extract and compounds 1, 2 and 7 showed significant cytotoxic activity against a HepG2 cell line. Full article

The compositions of 12 essential oils (EOs) obtained by hydrodistillation of edible fruits and herbs were analyzed by gas chromatography/mass spectroscopy (GC/MS). The insecticidal activity of each oil against the house fly Musca domestica was evaluated by placing flies in a glass jar with a screw cap that held a piece of EO-treated cotton yarn. The dose necessary to kill 50% of flies (LC₅₀) in 30 min was determined at 26 ± 1°C. Twelve EOs and 17 individual terpenes were assayed against M. domestica, showing LC₅₀ values ranging from 3.9 to 85.2 and from 3.3 to >100 mg/dm³, respectively. EO from Citrus sinensis was the most potent insecticide (LC₅₀ = 3.9 mg/dm³), followed by EOs from C. aurantium (LC₅₀ = 4.8 mg/dm³) and Eucalyptus cinerea (LC₅₀ = 5.5 mg/dm³). According to GC/MS analysis, limonene (92.47%), linalool (1.43%), and b-myrcene (0.88%) were the principal components of C. sinensis EO. Limonene was also the principal constituent (94.07%) of C. aurantium, while 1,8-cineole (56.86%) was the major constituent of E. cinerea EO. 1,8-Cineole was most active against M. domestica (LC₅₀ = 3.3 mg/dm³), while (4R)(+)-limonene, was moderately active (LC₅₀ = 6.2 mg/dm³). Dimethyl 2,2-dichlorovinyl phosphate (DDVP) selected as a positive control, showed an LC₅₀ of 0.5 mg/dm³. EOs from C. sinensis, C. aurantium, and E. cinerea show promise as natural insecticides against houseflies. Full article

Considering as a lead molecule the chemokine CXCR4 receptor antagonist AMD-3100, which shows significant anti-HIV activity in vitro and in vivo, we investigated a series of structurally related macrocyclic polyamines incorporating o,o’-phenanthroline or 2,2’-bipyridyl scaffolds as potential antiviral agents with lower toxicity and increased activity against both wild type X4-tropic and dual tropic HIV strains. The antiviral activity of these compounds was evaluated by susceptibility assays in PBMC (Peripheral Blood Mononuclear Cells) and compared to that of AMD-3100. The newly investigated compounds showed IC₅₀s values in the low micromolar range and significantly inhibited the viral replication of wild type X4-tropic isolate and dual tropic strains. These macrocyclic polyamines constitute a promising class of HIV entry inhibitors. Full article

The reaction of 3-mercaptopropylsilica (MPS) and chlorosulfonic acid in chloroform afforded silica bonded S-sulfonic acid (SBSSA), which was used as a catalyst for the room temperature synthesis of quinoxaline derivatives from 1,2-diamino compounds and 1,2-dicarbonyl compounds. The catalyst could be recycled and reused several times without any loss of efficiency. Full article

In this study a series ofnew1-(2-aryl-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanones 2a-e was synthesized by the cyclization of imines 1a-e using acetic anhydride. The products were evaluated for anti-bacterial and anti-fungal activity. Among the newly synthesized compounds, 1-(2-(4-(dimethylamino)phenyl)-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanone (2a)and1-(2-(4-chlorophenyl)-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanone (2b)were found to possess maximum activity against the tested strains of S. aureus and P. aeruginosa. It was concluded that para-substitution enhances the activity of synthesized oxadiazoles. Full article

One new sesquiterpene, (4E)-1-bromo-5-[(1'S*,3'R*)-3'-bromo-2',2'-dimethyl-6'-methylenecyclohexyl]-3-methylpent-4-ene-2,3-diol (1), and fifteen known sesquiterpenes, isopalisol (2), luzonensol (3), palisadin B (4), aplysistatin (5), palisadin A (6), 4-hydroxyl-palisudin C (7), 5-acetoxypalisadin B (8), 10-hydroxyaristolan-9-one (9), aristol-8-en-1-one (10), aristolan-9-en-1-one (11), aristolan-1(10)-en-9-one (12), aristolan-1(10)-en-9-ol (13), aristolan-1(10),8-diene (14), aristolan-1,9-diene (15) and aristofone (16), were isolated from a sample of marine red alga Laurencia similis. Their structures were established by detailed NMR spectroscopic analysis and comparison with literature data. Compounds 2-9, and 16 were isolated for the first time from this species. All these metabolites were submitted for a cytotoxicity assay against the tumor cell line BEL7402 (human liver adenocarcinoma), but all of them were found inactive (IC₅₀ > 10 μg/mL). Full article

Bacterial lipopolysaccharides (LPS), also known as endotoxins, are major structural components of the outer membrane of Gram-negative bacteria that serve as a barrier and protective shield between them and their surrounding environment. LPS is considered to be a major virulence factor as it strongly stimulates the secretion of pro-inflammatory cytokines which mediate the host immune response and culminating in septic shock. Quantitative structure-activity relationship studies of the LPS neutralization activities of anti-endotoxins were performed using charge and quantum chemical descriptors. Artificial neural network implementing the back-propagation algorithm was selected for the multivariate analysis. The predicted activities from leave-one-out cross-validation were well correlated with the experimental values as observed from the correlation coefficient and root mean square error of 0.930 and 0.162, respectively. Similarly, the external testing set also yielded good predictivity with correlation coefficient and root mean square error of 0.983 and 0.130. The model holds great potential for the rational design of novel and robust compounds with enhanced neutralization activity. Full article

Alkylation is a very important chemical reaction which modifies the biological properties of drugs. Quinazolinedione derivatives are of considerable interest due to their wide array of pharmacological properties.We now report application of a practical alkylation procedure to several quinazolinediones, including pelanserine (5f), which shows antihypertensive properties, 1-methyl-3-(2'-phenylethyl)-1H,3H-quinazoline-2,4-dione (1ab) and 1-methyl-3-[2'-(4'-methoxyphenyl)ethyl]-lH,3H-quinazoline-2,4-dione (1ae), which had been isolated from natural sources. The alkylation was optimized using dimethyl and diethyl carbonates under microwave irradiations. Full article

Traditional Chinese herbs are regarded as a new and promising source of potential anti-cancer remedies and new chemotherapy adjuvants to enhance the efficacy of chemotherapy and/or to ameliorate its side effects. Extensive investigations have been undertaken both in the experimental and clinical studies over the years to augment the efficacy of chemotherapy. Evodia rutaecarpa is a very popular multi-purpose herb traditionally used in China for the treatment of headaches, abdominal pain, postpartum hemorrhage, dysentery and amenorrhea. The major constituents of Evodia rutaecarpa are evodiamine and rutaecarpine. Growing evidence demonstrates that evodiamine possesses anti-cancer activities both in vitro and in vivo by inhibiting proliferation, invasion and metastasis, inducing apoptosis of a variety of tumor cell lines. This review is aimed to summarize the recent researches on evodiamine focusing on anti-cancer activity and to highlight molecular mechanisms during the past ten years. Full article

Several new acyclic ammonium-TFSI ionic liquids with an allyl substituent(s) were synthesized and their physicochemical and electrochemical properties were characterized. [AAMM]Am-TFSI (3) with two allyl groups showed the widest electrochemical stability window (5.9 V) among the ammonium-based ILs reported to date because of the increment of both the anodic and cathodic limits. The charge-discharge performance of a LiCoO₂-based half-cell containing [AAMM]Am-TFSI as an electrolyte was better in cycleability (the capacity retention ratio: 99% after 20 cycles) than that of the cell with the corresponding partially saturated analogue, [AMMP]Am-TFSI (2) (the capacity retention ratio: 92% after 20 cycles). Full article

Phytohormones, their functions, synthesis and effects, are of great interest. To study them in plant tissues accurate and sensitive methods are required. In the present study we aimed at optimizing experimental conditions to separate and determine not only plant hormones but also their metabolites, by liquid chromatography coupled with a UV-VIS detector. The mixture we analyzed was composed of benzyladenine, kinetin, trans-zeatin, cis-zeatin, dihydrozeatin, meta-topolin, ortho-topolin, α-naphthalene acetic acid, indole-3-acetic acid, trans-zeatin-7-glucoside, trans-zeatin-O-glucoside, trans-zeatin-9-riboside, meta-topolin-9-riboside and ortho-topolin-9-riboside. We measured the calibration dependences and estimated limits of detection and quantification under the optimal chromatographic conditions (column: Polaris C₁₈; mobile phase: gradient starting at 2:98 (methanol:0.001% TFA) and was increasing to 55:45 during twenty minutes, and then decreasing for 10 min to 35:65, flow rate: 200 µL·min^-1, temperature: 50 °C, wavelength: 210 nm). The detection limits for the target molecules were estimated as tens of ng per mL. We also studied the effect of flax extracts on the phytohormones’ signals. Recovery of aliphatic and aromatic cytokinins, metabolites of cytokinins and auxinswere within the range from 87 to 105 %. The experimental conditions were tested on a mass selective detector. In addition we analysed a commercial product used for stimulation of roots formation in cuttings of poorly rooting plants. The determined content of α-naphthalene acetic acid was in good agreement with that declared by the manufacturer. Full article

We have synthesized a number of phenoxypropylamines from N-{3-[3-(1-piperidinylmethyl)phenoxy]propyl}chloroacetamide (3). All the products have been characterized by elemental analysis, ¹H-NMR and MS. The biological activity effects of the title compounds were examined. From the biological activity results, we found that two of themshowed significant gastric acid antisecretory activity. Full article

Arils from six pomegranate (Punica granatum L.) varieties grown in the Mediterranean region of Turkey were tested for their antimicrobial properties by the agar diffusion and minimum inhibitory concentration (MIC) methods against seven bacteria: (Bacillus megaterium DSM 32, Pseudomonas aeruginosa DSM 9027, Staphylococcus aureus Cowan 1, Corynebacterium xerosis UC 9165, Escherichia coli DM, Enterococcus faecalis A10, Micrococcus luteus LA 2971), and threefungi (Kluvyeromyces marxianus A230, Rhodotorula rubra MC12, Candida albicans ATCC 1023). It has been observed that the pomegranate aril extracts had antimicrobial effect on all microorganisms, giving inhibition zones ranging in size from 13 to 26 mm. The MIC values for active pomegranate extracts ranged between 30 and >90 µg/mL. The results obtained appeared to confirm the antimicrobial potential of the Punica granatum varieties. Full article

Thiosemicarbazides are compounds known for their biological activity, particularly their antimicrobial properties, which include activity against fungi. The difficulty of treating fungal diseases induced us to assess the antifungal properties of some novel thiosemicarbazide compounds. We selected the natural products limonene and camphene as sources for the preparation of these new thiosemicarbazide derivatives. The compound N(4)-[2,2-dimethyl-3-methylnorbornane]-thiosemicarbazide (TIO C) showed an antifungal effect on Trichophyton mentagrophytes, with values of MIC = 55 mmol L^-1 and MFC = 110 mmol L^-1. Scanning-electron microscopy showed a decrease in mycelium development and morphological alterations of T. mentagrophytes cultured on nail fragments and treated with TIO C. In an attempt to discover its mode of action, we noted that ergosterol is apparently not a target of TIO C activity. An effect of TIO C on T. mentagrophytes cell walls and dividing cross-walls was shown by observed impairment of the fluorescence of tissues stained with calcofluor white, a specific marker for fungal chitin, suggesting that the compound can affect and damage the cell-wall structure or may interfere with its formation, during cell division, growth, and morphogenesis. This approach to the synthesis of new derivatives might provide interesting compounds with greater biological activity in pharmacological research. Full article

Three known flavones and seven known homoisoflavonoids were isolated from the methanolic extract of the leaves of Agave sisalanaPerrine ex Engelm. Their structures were elucidated on the basis of spectroscopic analysis. The isolated compounds were also evaluated for immunopharmacological activity. PBMC were used as target cells, and cell proliferation was determined by ³H-thymidine uptake. (±)-3,9-Dihydroeucomin (4), dihydrobonducellin (5), and 5,7-dihydroxy-3-(4′-hydroxybenzyl)-4-chromanone (7) showed inhibitory effects on PBMC proliferation activated by PHA with IC₅₀ values 19.4, 73.8, and 58.8 µM, respectively. All three compounds significantly inhibited the production of IL-2 and IFN-γ in activated PBMC in a concentration-dependent manner. Full article

Thenanofiltration of aqueous solutions of the ionic liquids (ILs) 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF₄), and 1-butyl-3-methylimidazolium bromide ([Bmim]Br) with a polyamide nanofiltration membrane was investigated. The practical transport coefficients, including hydrodynamic permeability (L_p), reflection (σ) and solute permeability (ω) were calculated in terms of a non-equilibrium thermodynamics approach. It was found that L_p and σ diminished as the concentration of the IL solutions increased. These characteristics are similar to those observed in inorganic electrolyte-water systems. In addition, it was shown that the rejection and volume flux for both ionic liquid solutions rose with feed pressure, while it decreased with feed concentration. The maximum rejection efficiencies for [Bmim]Br and [Bmim]BF₄ are 67 % and 60 %, respectively, on our experimental scale. All the data suggests that a highly efficient process for IL separation could be developed when the operating conditions are optimized further. Full article

Methyl gallate is a major component of Galla Rhois, as carvacrol is of oregano essential oils. Both have shown good antibacterial activity against intestinal bacteria. This study investigated the antibacterial activities of nalidixic acid in combination with methyl gallate and carvacrol against nalidixic acid resistant bacteria. The combined effect of nalidixic acid with methyl gallate and carvacrol was evaluated using the checkerboard method to obtain a fractional inhibitory concentration index. The results showed that the combinations of nalidixic acid + methyl gallate/carvacrol improved nalidixic acid resistant pathogenic bacteria inhibition with synergy or partial synergy activity. Thus, a strong bactericidal effect of the drug combinations was observed. In vitro data thus suggested that nalidixic acid combined with methyl gallate and carvacrol may be microbiologically beneficial, rather than antagonists. Full article

The preparation of a new type of derivatives of the naturally occurring antioxidant hydroxytyrosol is reported. Hydroxytyrosyl alkyl ethers were obtained in high yield by a three-step procedure starting from hydroxytyrosol isolated from olive oil waste waters. Preliminary results obtained by the Rancimat method have shown that these derivatives retain the high protective capacity of free hydroxytyrosol. Full article

New dissymmetric and asymmetric p-tert-butylthiacalix[4]arene derivatives were prepared as a result of the reaction of p-tert-butylthiacalix[4]arene with diethyl bromomalonate in the presence of different alkali metals (Cs, K and Na) in refluxing acetone for 7 days. The structures of the prepared compounds were investigated by IR, ¹H-NMR and MALDI-TOF mass spectroscopy. Full article

Five transition metal(II) complexes, [ML₂Cl₂] 1~5, were synthesized from the reaction of MCl₂·nH₂O (M = Mn, Co, Ni, Cu, Cd) and the Schiff base ligand 2-[(4-methylphenylimino)methyl]-6-methoxyphenol (C₁₅H₁₅NO₂, L), obtained by condensation of o-vanillin (2-hydroxy-3-methoxybenzaldehyde) with p-toluidine. They were characterized by elemental analysis, molar conductance, FT-IR spectra, thermal analysis. The structure of complex 1 was determined by single-crystal X-ray diffraction. Its crystal structure is of monoclinic system, space group P2₁/c with a = 9.0111(18) Å, b = 11.222(2) Å, c =28.130 (6) Å, α = 90 º, β = 92.29(3) º, γ = 90 º, V = 2867.6(10) ų, Z = 4. The Mn atom is six-coordinate and displays distorted octahedral geometry.The Schiff base ligand and its complexes have been tested in vitro to evaluate their antibacterial activity against bacteria, viz., Escherichia coli, Staphylococcus aureus and Bacillus subtilis. It has been found that the complexes have higher activity than the corresponding free Schiff base ligand against the same bacteria. Full article

In the present overview, we describe the bases of intercalation of small molecules (cationic and polar neutral compounds) in DNA. We briefly describe the importance of DNA structure and principles of intercalation. Selected syntheses, possibilities and applications are shown to exemplify the importance, drawbacks and challenges in this pertinent, new, and exciting research area. Additionally, some clinical applications (molecular processes, cancer therapy and others) and trends are described. Full article

Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and β-sitosterol (4)], together with the previously isolated individual compounds β-sitosterol (4), 2,4-di-tert-butylphenol (5), α-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC₅₀ value of 0.81µg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo. Full article

Essential oils extracted by hydrodistillation from the aerial parts and corollas of Origanum acutidens (Hand.-Mazz.) Ietswaart, an endemic Turkish flora species, were analyzed by GC-MS. The amounts of essential oil obtained from the aerial parts and the corollas were 0.73% and 0.93%, respectively. Twenty-five components in both the aerial parts oil and the corolla oil, representing 95.11% and 93.88%, respectively, were identified. The aerial parts and corolla oils were characterized by the predominance of two components: p-cymene (9.43% and 17.51%) and carvacrol (67.51% and 52.33%), respectively. The essential oils were also evaluated for their antimicrobial activity against ten bacteria by the disc diffusion assay. Our findings showed the following order in the sensitivity to the essential oils, as indicated by the corresponding inhibition zones: Proteus vulgaris > Salmonella typhimurium > Enterobacter cloacae > Klebsiella pneumonia > Escherichia coli > Serratia marcescens > Pseudomonas aeruginosa for the aerial parts essential oil, and Salmonella typhimurium > Proteus vulgaris > Enterobacter cloacae > Escherichia coli > Klebsiella pneumoniae > Serratia marcescens > Pseudomonas aeruginosa for the corolla essential oil. The studied essential oils thus exhibited a broad-spectrum of activity against both Gram-positive and Gram-negative bacteria, whereas the tested Gram-positive bacteria were more susceptible to the essential oil samples. Full article

Validation is a crucial aspect of quantitative structure–activity relationship (QSAR) modeling. The present paper shows that traditionally used validation parameters (leave-one-out Q² for internal validation and predictive R² for external validation) may be supplemented with two novel parameters r_m² and R_p² for a stricter test of validation. The parameter r_m²_(overall) penalizes a model for large differences between observed and predicted values of the compounds of the whole set (considering both training and test sets) while the parameter R_p² penalizes model R² for large differences between determination coefficient of nonrandom model and square of mean correlation coefficient of random models in case of a randomization test. Two other variants of r_m² parameter, r_m²_(LOO) and r_m²_(test), penalize a model more strictly than Q² and R²_pred respectively. Three different data sets of moderate to large size have been used to develop multiple models in order to indicate the suitability of the novel parameters in QSAR studies. The results show that in many cases the developed models could satisfy the requirements of conventional parameters (Q² and R²_pred) but fail to achieve the required values for the novel parameters r_m² and R_p². Moreover, these parameters also help in identifying the best models from among a set of comparable models. Thus, a test for these two parameters is suggested to be a more stringent requirement than the traditional validation parameters to decide acceptability of a predictive QSAR model, especially when a regulatory decision is involved. Full article

A simple and efficient route for preparing 2,3,5,6-tetraaminopyridine hydrochloride salt (TAP·3HCl·H₂O) was introduced in this paper. The title compound was synthesized, as usual, in two steps (nitration and hydrogenation) with a total yield of 90%. The use of an oleum and fuming nitric acid mixture in the nitration step improved the yield and purity of the intermediate product. A highly efficient hydrogenation using a H₂/Pd/C/C₂H₅OH system was developed. The products were characterized by TG, IR, ¹H-NMR, ¹³C-NMR, HPLC and elemental analysis. Full article