Characterization of Arabica and Robusta volatile coffees composition by reverse carrier gas headspace gas chromatography-mass spectrometry based on a statistical approach.

Nineteen samples of Arabica and 14 of Robusta coming from various plantation were analysed by dynamic headspace capillary gas chromatography-mass spectrometry to characterize the volatile fraction of green and roasted samples and the relationships of the same species with geographical origin. As concerns green beans, Arabica species appear characterized by high content of n-hexanol, furfural and amylformate, while Robusta species by greater content of ethylpyrazine, dimethylsulfone and 2-heptanone. Four variables, 4-methyl-2,3-dihydrofuran, n-hexanol, limonene and nonanal, appear involved in the characterization of the geographical origin of the analysed samples. The volatile fraction of the roasted Arabica samples, appear characterized by high content of pyridine, diacetyl, propylformate, acetone and 2,3-pentanedione, while Robusta samples by high content of methylbutyrate, 2,3-dimethylpyrazine and 3-hexanone. Considering geographical origin of the analysed samples, four compounds appear involved, in particular 2-butanone, methylbutyrate, methanol and ethylformate. Very accurate (error rate lower than 5%) rules to classify samples as Arabica or Robusta according to their compounds profile were developed.

Synthesis and controlled drug delivery studies of a novel Ubiquinol-Polyethylene glycol-Vitamin E adduct.

CoQ10 and Vitamin E are used in medicinal applications, but they are both lipophilic molecules and the poor solubility in aqueous media results in an inefficient administration, poor bioavailability and potential toxicity. A mixed conjugate Ubiquinol-Polyethylene glycol-Vitamin E was synthesized and characterized to improve the bioavailability of CoQ10 and Vitamin E. The synthesized mixed PEG conjugate was characterized by 1H NMR spectroscopy and MALDI spectrometry. The in vitro release of the conjugate was measured at various pH conditions and in human plasma and the evaluation of free CoQ10 and Vitamin E were also conducted. The obtained results demonstrated that more CoQ10 and Vitamin E were released from PEG conjugate at pH 7.4 and in plasma within the 24 h. The antioxidant activity evaluation was carried out by DPPH assay. Our results indicated that the chemical modification after esterification with PEG of the two drugs Ubiquinol and Vitamin E doesn't significantly affected their antioxidant potential.

Polysaccharides from Pleurotus eryngii var. elaeoselini (Agaricomycetes), a New Potential Culinary-Medicinal Oyster Mushroom from Italy.

Three water-soluble glucans (PELPS-A1, PELPS-A2, and PELPS-A3) purified from the hot water extract of the basidiomata of an edible mushroom Pleurotus eryngii var. elaeoselini by chromatography on DEAE-cellulose 32 and Sephadex G-100 column were found to consist of only D-glucose as monosaccharide constituent. Structural investigation was carried out by acid hydrolysis, periodate oxidation, and NMR experiments (1H-NMR, 13C-NMR, DQF-COSY, TOCSY, ROESY, HMQC, and HMBC). On the basis of these experiments, the structures of the repeating unit of the three isolated polysaccharides were established as follows: (1) PELPS-A1: {[→3)-α-D-Glcp-(1→]3→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→6)-α-D-Glcp-(1[→6)-ß-D-Glcp-(1→]2}n 6 ↑ 1 α-D-Glcp (2) PELPS-A2: [→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(1→]n 3 ↑ 1 ß-D-Glcp (3) PELPS-A3: [→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→6)-α-D-Glcp-(1→]n The dried basidiomata of P. eryngii var. elaoselini were tested for their antioxidant activity by DPPH and hydroxyl radical scavenging assays. The crude extract has shown a SC50 of 1.4 mg/mL for DPPH test while a SC50 of 5.7 mg/mL was observed for hydroxyl radical scavenging activity test. The antioxidant activity of PELPS-A1, PELPS-A2, and PELPS-A3, evaluated as hydroxyl radical scavenging activity, was similar and significant, suggesting their use as antioxidants.

Imidazole and 1,2,4-Triazole-based Derivatives Gifted with Antitubercular Activity: Cytotoxicity and Computational Assessment.

BACKGROUND: Mycobacterium Tuberculosis (Mtb) is the causative pathogen of Tuberculosis (TB) and outbreaks are more common among immunosuppressed persons infected with HIV. The current treatment regimens are lengthy and toxic, yet the therapy has remained unchanged for many decades, so there is a need to find new structures with selective mechanism of action. Moreover, the increased incidence of severe disseminated infections produced by undiagnosed Multidrug-resistant (MDR), worsen clinical treatment and contribute the spread of the disease. OBJECTIVE: The aim of our study was to evaluate the potential of imidazole and triazole moieties for antimycobacterial activity, by synthesizing some 1-(1-(aryl)-2-(2,6-dichlorophenyl)hydrazono)ethyl- 1H-imidazole and 1H-1,2,4-triazole derivatives 2a-l. METHODS: The title compounds were obtained via classical organic synthesis. The antimicrobial activity was evaluated using the method of microdilution and the cytotoxicity assay was performed by MTT method. RESULTS: The results indicated that the presence of both the imidazole ring and that of the 2,6- dichlorosubstituted phenyl moiety, is more relevant for inhibitory activity against Mtb than the triazole nucleus and the unsubstituted phenyl ring. Among the series, (E)-1-(2-(5-chlorothiophen-2-yl)-2-(2- (2,6-dichlorophenyl)hydrazono)ethyl)-1H-imidazole derivative 2f and (Z)-1-(2-([1,1'-biphenyl]-4-yl)- 2-(2-(2,6-dichlorophenyl)hydrazono)ethyl]-1H-imidazole derivatives 2e exhibited a promising antimycobacterial property and the latter also displayed a safe cytotoxic profile. CONCLUSION: The synthesized compounds were studied for their antitubercular activity. Among the series, the compounds 2e and 2f appeared to be the most promising agents and, according to the docking assessment, the compounds could be CYP51 inhibitors. These evidences could be useful for the future development of new antimycobacterial derivatives targeting CYP51 with more specificity for the mycobacterial cell enzyme.

Structural Characterization of Polysaccharides of a Productive Strain of the Culinary-Medicinal King Oyster Mushroom, Pleurotus eryngii (Agaricomycetes), from Italy.

A preliminary biological investigation of the dry basidiomata of strain C-142-c of Pleurotus eryngii has shown significant antioxidant activity. Two different polysaccharides (PEPS-A1 and PEPS-A2) were isolated from the cultivated edible mushroom, P. eryngii C-142-c strain. Based on acid hydrolysis, methylation analysis, and nuclear magnetic resonance experiments (1H, 13C, distortionless enhancement by polarization transfer, double quantum filtered correlation spectroscopy, total correlation spectroscopy, nuclear Overhauser effect spectroscopy, heteronuclear single-quantum correlation spectroscopy, and heteronuclear multiple-bond correlation spectroscopy), the structures of the repeating unit of PEPS-A1 and PEPS-A2 were established as follows: (l)PEPS-Al (α-glucan): [→6)-α-D-Glcp-(1→6)-α-D-Glcp-(l→]n; and (2) PEPS-A2 (ß-glucan): [→6)-ß-D-Glcp-(1→6)-ß-D-Glcp-(l→]n. The antioxidant activity of PEPS-A1 and PEPS-A2 was evaluated as hydroxyl radical scavenging activity. PEPS-A1 and PEPS-A2 showed SC50 values of 400 µg/mL and 122 µg/mL, respectively, suggesting their possible use as a dietary supplement in functional foods. The polysaccharides were tested for their activity on cell viability using a colorectal adenocarcinoma cell line (HT-29). Both polysaccharides affected cell viability after 48 and 72 hours of treatment, inducing the death of 50% of HT-29 cells between 0.25 and 1 µg/mL and between 0.5 and 1 µg/mL, respectively, for PEPS-A1 and PEPS-A2. These results are promising for future applications of these mushroom-derived polysaccharides as antioxidants and antitumor agents.

Improvement of Chemical and Physical Properties and Antioxidant Evaluation of Eugenol - PEG adduct.

Eugenol (EU) - PEG adduct was synthesized to improve the chemical and physical properties of eugenol. The phenolic group was covalently bound to the carboxyl group of PEG and the release kinetics were studied in vitro in buffer solution at pH 7.4, in simulated gastric fluid and in mouse plasma. Studies in vitro on the release of the parent drug from the prodrug in various media indicate that the adduct may be sufficiently stable to pass intact into the gastrointestinal tract and release EU into the circulation. The antioxidant activity of PEG-EU adduct was also evaluated. Scavenging activity was absent in the original PEG-EU adduct but gradually increased on the basis of drug delivery.

Antioxidant Properties of Oak Bracket Mushroom, Pseudoinonotus dryadeus (Higher Basidiomycetes): A Mycochemical Study.

A complex mixture of free fatty acids (1), cerevisterol (2), a sphingosine (3), and a complex mixture of diacylglycerophospholipids (4) were isolated from the fruiting body of the basidiomycete mushroom Pseudoinonotus dryadeus and subjected to spectroscopic analyses. The antioxidant activities of the whole extract of the fungus, of the isolated fractions, and of compounds 1-4 were evaluated in two in vitro model systems: 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and superoxide anion. In each systems, the extract of fungus and compound 2 showed the same free radical scavenging activity (with SC50 data of 18.27 µg/mL and 5.75 µg/mL, respectively) compared with the positive control quercetin (DPPH assay). Compounds 1-4 were isolated from P. dryadeus for the first time.

PEG-Ursolic Acid Conjugate: Synthesis and In Vitro Release Studies.

A highly water-soluble macromolecular compound of ursolic acid with monomethoxypoly(ethylene glycol) (mPEG) was prepared. The physicochemical properties and stabilities under different conditions were investigated. By PEG conjugation, greatly increased water solubility was obtained, and the results showed that this conjugate was a potential prodrug for the oral delivery of ursolic acid.

Chemical composition and functional characterisation of commercial pumpkin seed oil.

BACKGROUND: Pumpkin (Cucurbita pepo L.) seed oil is a common product in Slovenia, Hungary and Austria and is considered a preventive agent for various pathologies, particularly prostate diseases. These properties are related to its high content of carotenoids and liposoluble vitamins. In this study the carotenoid (lutein and zeaxanthin), vitamin E (α- and γ-tocopherol) and fatty acid contents of 12 samples of commercial pumpkin seed oil were investigated together with the composition of the volatile fraction resulting from the roasting process. RESULTS: The aromatic profile obtained from the commercial samples was directly related to the intensity of the roasting process of the crushed pumpkin seeds. The roasting temperature played a crucial role in the concentrations of volatile substances originating from Strecker degradation, lipid peroxidation and Maillard reaction. CONCLUSION: The findings suggest that high-temperature roasting leads to the production of an oil with intense aromatic characteristics, while mild conditions, generally employed to obtain an oil with professed therapeutic characteristics, lead to a product with minor characteristic pumpkin seed oil aroma. The nutraceutical properties of the product are confirmed by the high content of α- and γ-tocopherol and carotenoids.

Pharmacokinetic analysis of multi PEG-theophylline conjugates.

In the attempt of prolonging the effect of drugs, a new branched, high-molecular weight multimeric poly(ethylene glycol) (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as drug carrier. In particular, the attention was focused on the study of theophylline (THEO) and THEO-MultiPEG conjugates pharmacokinetic after oral administration in rabbit. Pharmacokinetic behavior was studied according to an ad hoc developed mathematical model accounting for THEO-MultiPEG in vivo absorption and decomposition into drug (THEO) and carrier (MultiPEG). The branched high-molecular weight MultiPEG proved to be a reliable drug delivery system able to prolong theophylline staying in the blood after oral administration of a THEO-MultiPEG solution. The analysis of experimental data by means of the developed mathematical model revealed that the prolongation of THEO effect was essentially due to the low THEO-MultiPEG permeability in comparison to that of pure THEO.

Bioactive lipids metabolites in Amanita virosa.

Thrombin is the key serine proteinase of the coagulation cascade and, therefore, a suitable target for inhibition of blood coagulation. An extract of Amanita virosa considerably inhibited thrombin (48%), but showed no inhibitory activity on trypsin. On the basis of inhibition selectivity between thrombin and trypsin and potency of thrombin inhibition, A. virosa constitutes a good starting material for the isolation of further compounds that are active against thrombin. Bioassay oriented fractionation of the extract of A. virosa led to the isolation of a complex mixture of triglycerides (TGs), monoacylglycerols (MAGs), free fatty acids (FAs) and ergosterol. The structures of the isolated lipids metabolites were determined on the basis of chemical and spectroscopic evidences.

Conjugated PDT drug: photosensitizing activity and tissue distribution of PEGylated pheophorbide a.

The design of new photosensitizers with enhanced phototoxicity and pharmacokinetic properties remains a central challenge for cancer photodynamic therapy (PDT). In this study, Pheophorbide a (Pba) has been pegylated to methoxypolyethylene glycol (mPE G-Pba) to produce a soluble photosensitizer that exhibits a higher tissue distribution than free Pba. In vitro studies have shown that mPE G-Pba promotes a fairly strong photosensitizing effect in cancer cells, as previously observed for the unpegylated molecule. mPE G-Pba targets the mitochondria where, following photoactivation, ROS are produced which cause a cellular injury by lipid peroxidation. The effect of pegylation on the photosensitizer biodistribution has been examined in different selected organs of female mice, at different time points after intraperitoneal administration of the drug (50 µmol/Kg body weight). Other than free Pba, which showed a low tissue accumulation, mPE G-Pba has been detected in significant amounts (8 to 16 µg/ml) in liver, spleen, duodenum and kidney and, 3-5 hours after intraperitoneal injection, in moderate amounts (3 to 8 µg/ml) in brain and lung. In vivo optical imaging performed on living female C57/BL6 mice bearing a subcutaneous melanoma mass, showed that injected mPEG-Pba distributes all over the body, with an higher uptake in the tumor respect to free Pba. Our results indicate that although pegylation somewhat decreases the phototoxicity, it significantly increases the drug solubility and tissue distribution and tumor uptake of mPE G-Pba, making the conjugate an interesting photosensitizer for PDT.

Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand-receptor recognition process.

A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA(3) AR (range 311-633nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA(2B) AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC(50) 3.42microM) and could represent a starting point for searching new non-xanthine hA(2B) AR antagonists. Molecular models of the rA(2A) and hA(3) ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided.

Cerebrosides with antiproliferative activity from Euphorbia peplis L.

Two new cerebrosides have been isolated from the whole plants of Euphorbia peplis L. The structures were established by FT-IR spectroscopy, FAB MS, EI-MS, ESI-MS, 1D and 2D NMR spectroscopy. The structures of the cerebrosides were characterized as 1-O-beta-d-glycosides of phytosphingosines, which comprised a common long-chain base, (2S, 3S, 4R, 8Z)-2-amino-8 (Z)-octadecene-1,3,4-triol with 2-hydroxy fatty acids of varying chain lengths (C25, C22) linked to the amino group. The isolated compounds were shown to possess significant antiproliferative properties against cultured human tumor cell lines KB and IMR-32.

Synthesis of 4-thiophen-2'-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel.

The gating of the CFTR chloride channel is altered by a group of mutations that cause cystic fibrosis. This gating defect may be corrected by small molecules called potentiators. Some 1,4-dihydropyridine (DHP) derivatives, bearing a thiophen-2-yl and a furanyl ring at the 4-position of the nucleus, were prepared and tested as CFTR potentiators. In particular, we evaluated the ability of novel DHPs to enhance the activity of the rescued DeltaF508-CFTR as measured with a functional assay based on the halide-sensitive yellow fluorescent protein. Most DHPs showed an effect comparable to or better than that of the reference compound genistein. The potency was instead significantly improved, with some compounds, such as 3g, 3h, 3n, 4a, 4b, and 4d, having a half effective concentration in the submicromolar range. CoMFA analysis gave helpful suggestions to improve the activity of DHPs.

Chemoenzymatic synthesis and antimicrobial activity evaluation of monogalactosyl diglycerides.

Monogalactosyl diglycerides with medium to long fatty acid acyl chains, were prepared and examined for antimicrobial activity against Gram positive, Gram negative bacteria and fungi. The study of their in vitro antimicrobial activity confirms the significant activity of some monogalactosyl diacylglycerol analogues and establishes for the galactose series that the 1,2-disubstitution and the octanoyl chain are the proper structural features for the maximum activity.

A simple method for the preparation of PEG-6-mercaptopurine for oral administration.

A new and efficient method for the synthesis of PEG-6-mercaptopurine is described. The key feature of the proposed approach is the protection of the thiol group against metabolic inactivation. Preliminary in vivo and in vitro evaluations of the macromolecular prodrug have been carried out.

New biologically active epidioxysterols from Stereum hirsutum.

From the fungus Stereum hirsutum have been isolated and identified two new epidioxysterols 1, 4, together with two known ones 2 and 3. Their structures were elucidated on the basis of spectroscopic analysis and chemical reactions. Epidioxysterols 1-4 have been shown to possess a significant activity against Mycobacterium tuberculosis.

Chemoenzymatic synthesis and in vitro studies on the hydrolysis of antimicrobial monoglycosyl diglycerides by pancreatic lipase.

Monoglucosyl and monogalactosyl diglycerides (MGDGs) with medium-long length acyl chains, identified as active components in Euphorbiaceae, were synthesized. They were examined for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. MGDGs with two octanoyl groups at both 1- and 2-positions showed the most potent activity. The stereoselectivity of pancreatic lipase was investigated in vitro where the preference for the 1 position in MGDGs is strictly related to the length of the acyl chains.

New MultiPEG-conjugated theophylline derivatives: synthesis and pharmacological evaluations.

The successful conjugation of active theophylline molecules to two new multifunctional high-molecular weight poly(ethylene glycol) derivatives (MultiPEG) and their pharmacokinetic evaluations are reported. The drug loading was increased up to six times in comparison with commercial PEG of the same molecular weight. A clear increase of the time of persistence within the body and a concomitant improvement of the overall pharmacokinetic properties of those prodrugs were also observed. These studies sustain the use of these new PEG-based polymeric supports as a valuable alternative for an effective drug delivery system.