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Hovenia dulcis Thunberg is an herbal plant, belonging to the Rhamnaceae family, widespread in west Asia, USA, Australia and New Zealand, but still almost unknown in Western countries. H. dulcis has been described to possess several pharmacological properties, such as antidiabetic, anticancer, antioxidant, anti-inflammatory and hepatoprotective, especially in the hangover treatment, validating its use as an herbal remedy in the Chinese Traditional Medicine. These biological properties are related to a variety of secondary metabolites synthesized by the different plant parts. Root, bark and leaves are rich of dammarane-type triterpene saponins; dihydrokaempferol, quercetin, 3,3′,5′,5,7-pentahydroflavone and dihydromyricetin are flavonoids isolated from the seeds; fruits contain mainly dihydroflavonols, such as dihydromyricetin (or ampelopsin) and hovenodulinol, and flavonols such as myricetin and gallocatechin; alkaloids were found in root, barks (frangulanin) and seeds (perlolyrin), and organic acids (vanillic and ferulic) in hot water extract from seeds. Finally, peduncles have plenty of polysaccharides which justify the use as a food supplement. The aim of this work is to review the whole scientific production, with special focus on the last decade, in order to update phytochemistry, biological activities, nutritional properties, toxicological aspect and regulatory classification of H. dulcis extracts for its use in the European Union.

A combination of flash chromatography, solid phase extraction, high-performance liquid chromatography, and in vitro bioassays was used to isolate phytocomponents endowed with anticholinesterase activity in extract from Phyllanthus muellarianus. Phytocomponents responsible for the anti-cholinesterase activity of subfractions PMF1 and PMF4 were identified and re-assayed to confirm their activity. Magnoflorine was identified as an active phytocomponent from PMF1 while nitidine was isolated from PMF4. Magnoflorine was shown to be a selective inhibitor of human butyrylcholinesterase—hBChE (IC50 = 131 ± 9 μM and IC50 = 1120 ± 83 μM, for hBuChE and human acetylcholinesterase—hAChE, respectively), while nitidine showed comparable inhibitory potencies against both enzymes (IC50 = 6.68 ± 0.13 μM and IC50 = 5.31 ± 0.50 μM, for hBChE and hAChE, respectively). When compared with the commercial anti-Alzheimer drug galanthamine, nitidine was as potent as galanthamine against hAChE and one order of magnitude more potent against hBuChE. Furthermore, nitidine also showed significant, although weak, antiaggregating activity towards amyloid-β self-aggregation.

Affinity-based methods using immobilized proteins are important approaches for understanding the interactions between small molecules and biological targets. This review is intended to provide an overview of different affinity based separation methods that have been applied to the study of peroxisome proliferator activated receptors (PPARs). The screening of compound to increase screening rates for synthetic and natural ligands of PPAR are reported. Pros and cons of the approaches in ligand discovery initiatives are discussed.

Phyllanthus muellerianus (Kuntze) Excell (family Euphorbiaceae) stem bark methanol extract inhibited the growth of Clostridium sporogenes and Streptococcus pyogenes, responsible for gas gangrene and suppurative and non suppurative diseases, respectively. After the HPLC fingerprint acquisition a bioguided fractionation of the defatted methanol extract allowed the isolation of six fractions whose activity was evaluated against the two pathogen bacteria. A further purification of the most active fraction afforded a pure compound responsible for the very interesting inhibitory activity against C. sporogenes and S. pyogenes (MIC 0.91 μM, MIC 3.64 μM). (1)H NMR and MS analytical techniques allowed the identification of the bioactive as Nitidine; this quaternary ammonium alkaloid was observed in the genus Phyllanthus for the first time. A study on Nitidine counter ion, performed using energy dispersive spectroscopy (EDS) coupled with scanning electron microscopy (SEM) was also carried out.

Bellevalia saviczii is a medicinal plant used as anti-rheumatic and anti-inflammatory herbal remedy in Iraqi-Kurdistan. The aim of this study was to evaluate the anti-inflammatory activity of its extract and the isolated homoisoflavonoid (Dracol) by studying the Ca2+-dependent NF-kB pathway. Nuclear translocation of p65 NF-kB subunit, as parameter of NF-kB activation, was visualized in human leukemic monocytes by immunofluorescence and Western blot analyses, after cell treatment with B. saviczii root extract or Dracol followed by Lipopolysaccharide stimulation. In parallel, Ca2+ signals responsible for NF-kB activation and levels of inflammatory cytokines were investigated. LPS-induced p65 translocation was evident in monocytes and both treatments, in particular that with Dracol, were able to counteract this activation. Intracellular Ca2+ oscillations were halted and the cytokine release reduced. These results confirm the traditional anti-inflammatory efficacy of B. saviczii and identify one of the molecules in the extract which appears to be responsible of this action.

Hydrodistillation of Xylopia hypolampra Mildbr. stem bark afforded 39 mg (dry weight basis) of a pale yellow fragrant essential oil; gas chromatography-flame ionization detector and gas chromatogra...

Ethnopharmacological relevance Allanblackia floribunda Oliv. is one of the most commonly used medicinal plant in Cameroon. The stem bark of the plant is traditionally used for its aphrodisiac and antihypertensive properties. Aim of the study To validate the traditional uses of Allanblackia floribunda stem bark ethanol extract through the evaluation of their aphrodisiac and vasorelaxant properties. Materials and methods The extract's ability to increase sexual desire and the frequencies of erection (mount), intromission and prolonged latency of ejaculation were studied on adult male rats. The vasodilator effect was investigated using isolated rat aorta rings. Tests were conducted using fractions obtained by reverse phase column-chromatography (CC), after the acquisition of the HPLC fingerprint of the ethanol extract, resulted the most active in previous studies. Results The CC allowed the isolation of five fractions whose aphrodisiac and vasodilator activities were tested and compared with those of the whole extract. Four compounds were identified and characterized, three of them, Fukugiside, Morelloflavone and Volkensiflavone, are secondary metabolites known to be in Allanblackia floribunda; the fourth, Spicataside, is a biflavonoid glycoside known to be present in the genus Garcinia but never found neither in Allanblackia floribunda nor in Allanblackia genus. The crude ethanolic extract (CEE) induced a relaxation on aorta rings with EC 50 =11±2 μg/mL and Morelloflavone displayed a similar activity with EC 50 =42±6 μg/mL; for all the other compounds only the vasodilation % at the maximum concentration assessable (90 μg/mL) was determined: 30±8 (Fukugiside), 24±6 (Spicataside), 33±4 (Morelloflavone+Volkensiflavone), 47±1 (Volkensiflavone). Regarding the activity on male sexual behaviour, only CEE and Fukugiside showed activity in the 9 parameters evaluated. Conclusions These results may support the traditional uses of Allanblackia floribunda as aphrodisiac plant with antihypertensive properties suggesting the phytocomplex as responsible for the claimed activity.

Ethnopharmacological relevance Drypetes klainei Pierre ex Pax is used in Cameroon by Baka Pygmies in the wound healing process and for the treatment of burns. Aim of the study To validate the traditional use of D. klainei Pierre ex Pax stem bark extracts through the evaluation of their antimicrobial properties and their ability to improve wound healing process in fibroblast cell cultures. Materials and methods The antimicrobial properties of D. klainei extracts were evaluated against Staphylococcus aureus ATCC 6538, Streptococcus pyogenes ATCC 19615, Escherichia coli ATCC 10536, Candida albicans ATCC 10231, on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal–fungicidal concentration (MBC–MFC) by the macrodilution method. The extracts abilities to accelerate wound healing were studied on murine and human fibroblasts in terms of cell viability and migration (scratch wound-healing assay). Results All the extracts were non-toxic against the selected microorganisms at the tested concentrations, and significantly improve wound healing process in vitro, compared to untreated controls. However, the defatted methanol extract was active at lower concentrations, compared to the water extract. Conclusions The ability of both water and defatted methanol extracts to accelerate scratch wound closure in fibroblast cultures may support the traditional use of D. klainei stem bark in the treatment of skin lesions (such as burns) even if no antimicrobial activity was evidenced.

In the present paper, we report on the synthesis and antinociceptive activity of a new series of N-methyl-arylpyrrolidinols that we designed for a rational structure-activity relationship (SAR) study. The antinociceptive properties were investigated in vivo by the hot plate and formalin tests in mice and control on the locomotory activity was also monitored by the rota rod test. With this aim, the evaluation of the lipophilicity of all compounds was performed by the Daylight computational method in order to better understand the SAR. Interesting properties were proven for the compounds of the entire series.

The phytochemical research based on ethnopharmacology is considered an effective approach in the discovery of novel chemicals entities with potential as drug leads. Plants/plant extracts/decoctions, used by folklore traditions for treating several diseases, represent a source of chemical entities but no information are available on their nature. Starting from this viewpoint, the aim of this review is to address natural-products chemists to the choice of the best methodologies, which include the combination of extraction/sample preparation tools and analytical techniques, for isolating and characterizing bioactive secondary metabolites from plants, as potential lead compounds in the drug discovery process. The work is distributed according to the different steps involved in the ethnopharmacological approach (extraction, sample preparation, biological screening, etc.), discussing the analytical techniques employed for the isolation and identification of compound/s responsible for the biological activity claimed in the traditional use (separation, spectroscopic, hyphenated techniques, etc.). Particular emphasis will be on herbal medicines applications and developments achieved from 2010 up to date.

The diastereoselective synthesis of naphthyl amino alcohols via nucleophilic addition to racemic 1-dimethylamino-2-methylpentan-3-one was studied. The use of the appropriate experimental conditions allowed the synthesis of both diastereoisomers. The relative configurations were established via NOESY experiments.

Optically pure 2-tributylstannyl-N-Boc-1,3-oxazolidine 6 , prepared from the camphor-derived aminoalcohol 5 , was converted to diastereomerically pure 2-acyl derivatives 8 in three steps. Reaction of these ketones with Grignard reagents at −78°C proceeded with high stereoselectivity affording tertiary carbinols which gave 1,2-diols with >96% ee after hydrolysis and reduction of the intermediate α-hydroxy aldehydes. A new deblocking procedure of the t-Boc group is also described.

Ethnopharmacological relevance Diospyros bipindensis (Gurke) stem bark is used in Cameroon by Baka Pygmies for the treatment of respiratory disorders. Aim of the study To assess the anti-inflammatory, antibacterial and antioxidant properties of constituents from the bark extracts through bioassay-guided fractionation. Materials and methods The anti-inflammatory activity of extracts, fractions and pure compounds was assessed through the inhibition of the pro-inflammatory mediator nuclear factor-kappa B (NF-κB) transcriptional activity and nitric oxide (NO) production. DPPH, ABTS and ORAC assays were used for determining the antioxidant properties. The activity against Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Klebsiella pneumoniae , was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by the macrodilution method. Results The water extract showed antimicrobial activity against S. pneumoniae (MIC: 300 μg/ml) and S. pyogenes (MIC: 300 μg/ml). The dichloromethane extract efficiently inhibited NF-κB transcriptional activity and NO production and exhibited significant antioxidant activity in the ORAC assay. An interesting activity was also found against S. pneumoniae (MIC: 200 μg/ml), S. aureus (MIC: 400 μg/ml) and S. pyogenes (MIC: 200 μg/ml). The phytochemical investigation of the dichloromethane extract afforded plumbagin, canaliculatin, ismailin, betulinic acid and 4-hydroxy-5-methyl-coumarin as the main constituents. Plumbagin and ismailin were found to be responsible for the main biological activities observed. Conclusions These results may provide a rational support for the traditional use of Diospyros bipindensis stem bark in the treatment of respiratory disorders, since the anti-inflammatory, antimicrobial and antioxidant compounds isolated from the dichloromethane extract were also present in the traditional water extract.

Ethnopharmacological relevance Phyllanthus muellerianus (Kuntze) Excel (family Euphorbiaceae) stem bark is used in Cameroon by Baka pygmies as a remedy for wound healing and tetanus. Aim of the study To characterize the chemical composition and to evaluate the antimicrobial properties of the essential oil of the plant. Materials and methods The essential oil was extracted from the stem bark by dynamic head space and by hydrodistillation and characterized by GC and GC-MS analyses. The antimicrobial activity was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal–fungicidal concentration (MBC–MFC) by the micro and macrodilution methods. The following bacteria and fungi were used: Clostridium sporogenes ATCC 3584, Staphylococcus aureus ATCC 6538, Streptococcus mutans ATCC 25175, Streptococcus pyogenes ATCC 19615, Escherichia coli ATCC 10536, Candida albicans ATCC 10231, Candida albicans LM 450, Trichophyton mentagrophytes LM 230, Trichophyton rubrum LM 237, Microsporum canis LM 324. Results The hydrodistillation afforded 0.06% (dry weight basis) of pale yellow oil. Thirty-eight compounds representing 90.69% were identified. The major component (36.40%) was found to be (E)-isoelemicin, identified by comparison of its 1H-NMR experimental data, with literature data. The oil showed good antibacterial activity against Clostridium Sporogenes, Streptococcus mutans and Streptococcus pyogenes with MIC ranging from 13.5 to 126 μg/ml. A weak antifungal activity (MIC 250 μg/ml) was found against Trichophyton rubrum, only. Conclusions The antimicrobial activity and the chemical composition of Phyllanthus muellerianus stem bark essential oil are reported for the first time.

The preparation of enantiomerically pure 2-lithio-1,3-dioxolanes and 2-lithiooxazolidines and their use as formyl anion equivalents in addition reactions to aldehydes are described.

Ethnopharmacological relevance The plants of the genus Phyllanthus (Euphorbiaceae) are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat several diseases. Particularly, Phyllanthus muellerianus (Kuntze) Excell, commonly called “mbolongo” in Cameroon, is used by pygmies baka as a remedy for tetanus and wound infections. Aim of the study To investigate the antimicrobial properties of Phyllanthus muellerianus (Kuntze) Excell (family Euphorbiaceae) stem bark used in Cameroon by baka pygmies as a remedy for wound healing and tetanus. Materials and methods Aqueous and methanol extracts with and without defatting treatment, were prepared and their activity against Clostridium sporogenes ATCC 3584, Staphylococcus aureus ATCC 6538, Streptococcus mutans ATCC 25175, Streptococcus pyogenes ATCC 19615, Escherichia coli ATCC 10536, Candida albicans ATCC 10231, was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal-fungicidal concentration (MBC-MFC) by the macrodilution method. Results Water extract showed a weak activity against Clostridium sporogenes (MIC 900 μg/mL) and resulted inactive at the tested concentrations against all the other microorganisms. The defatted methanol extract, inactive against Staphylococcus aureus , Escherichia coli , Candida albicans , exhibited a very interesting activity against Clostridium sporogenes and Streptococcus pyogenes (MIC 100 μg/mL and 300 μg/mL, respectively), which seems to validate the use of this plant in pygmies traditional medicine for the treatment of tetanus and wound infections. The activity found against Streptococcus mutans (300 μg/mL), aetiological agent of caries, may suggest a possible use of this plant as natural remedy to prevent dental diseases. Conclusions The activity against streptococci and Clostridium sporogenes ATCC 3584, showed by stem bark extracts of Phyllanthus muellerianus , traditionally used by baka pygmies to treat wound infections and tetanus, is reported for the first time.

Aim of the study Bridelia grandis (Pierre ex Hutch) (Euphorbiaceae) is a medicinal plant traditionally used in Cameroon by pygmies Baka as a remedy for oral cavity affection. Bioassay-guided stem bark extracts were investigated for their in vitro antimicrobial properties as well as their phytochemical constituents. Materials and methods The first extraction was carried out according to the traditional use. Further extractions were carried out with solvents of different polarity such as methanol (MeOH), ethyl acetate (EtOAc) and mixtures of MeOH–H 2 O. The antimicrobial activity of the extracts against oral Streptococci was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by the macrodilution method; the bacterial surface hydrophobicity was also evaluated. Results Water, methanol and mixtures methanol–water extracts, exhibited antibacterial activity with MIC between 0.5 and 2 mg/ml justifying the traditional use of Bridelia grandis stem bark for oral cavity affection. Preliminary phytochemical analysis was performed on the most active extract (methanol) using appropriate tests and well established analytical screening methods, such as TLC and RP-HPLC/DAD. Conclusions The data obtained indicate that tannins constitute the chemical family responsible for the biological activity.

The chiral recognition mechanism of Penicillin G Acylase (PGA) was investigated with a set of 18 new chiral acidic compounds. A series of 2-aryloxyalkyl- and 2-arylalkyl-2-aryloxyacetic acids in which the absolute configuration has been reported to exert a strong influence on pharmacological activity, were synthesized and analysed on PGA-based chiral stationary phase (CSP) and 11 racemates were completely resolved with a mobile phase composed of 50 mM phosphate buffer (pH 7.0). The influence of structural variations of analytes on retention and enantioselectivity was investigated by application of molecular modelling studies. Docking experiments were also carried out to rationalize the observed enantioselective behaviour. The computation approach revealed to be helpful in elucidating the molecular basis of the enantioselectivity observed on PGA-CSP.

The development and characterization of an anti-aflatoxin B1 (anti-AFB1) immunoaffinity monolithic disk is reported. Polyclonal anti-AFB1 was covalently immobilized in batch on an epoxy-activated monolithic Convective Interaction Media (CIM) disk (12 mm × 3 mm i.d.) by a one-step reaction via epoxy groups of the polymer surface. 0.96 mg of antibody were immobilized and the binding capacity of the CIM disk was determined by frontal analysis. The CIM disk was coupled through a switching valve to a reversed-phase column, namely Chromolith Performance RP-18e. A fully automated HPLC method with fluorescence detection for the determination of aflatoxin B1 in aqueous solution was developed. The total analysis time with the integrated system is 46 min and the retention time of AFB1 is approximately 29 min. The binding capacity of the immunoaffinity disk was evaluated in terms of linearity, precision and accuracy of the extraction procedure. The immunoaffinity support was stable after repeated runs.

Since the early days of combinatorial chemistry solid-phase organic synthesis has been the method of choice for the production of large libraries. Solution-phase synthesis is again gaining importance especially for the synthesis of parallel arrays of smaller, focussed libraries containing single compounds with high degrees of purity. In the field of solution-phase library generation, the use of solid-supported reagents, catalysts and scavengers is emerging as a leading strategy, combining the advantages of both solid-phase organic synthesis (e.g. allowing the employment of an excess of reagent without the need for additional purification steps) and solution-phase chemistry (e.g. the ease of monitoring the progress of the reactions by applying LC-MS, TLC or standard NMR techniques). An account of some of the most recent advances in this area of research will be presented.

A flexible stereoselective synthetic scheme was developed to prepare 6,5-fused bicyclic lactams, that molecular mechanics calculations revealed to have a potential as reverse-turn mimetics. The convergence of the synthetic sequence was achieved by attachment of a properly substituted malonate unit to the (2S)-cis-5-(2-hydroxyethyl)proline tert-butyl ester. Stereoselective intramolecular alkylation of the malonate afforded the 6-membered lactam fused to the 2-carbalkoxy pyrrolidine nucleus. X-ray diffraction analysis of a more advanced synthetic derivative allowed the unequivocal assignment of the configuration at the newly created quaternary stereocenter as R.