Synergism of crude extracts and essential oils from medicinal plants with antimicrobial drugs

The emergence of resistant strains to conventional antimicrobial drugs has been constant as well as research aimed new alternatives of antibacterial agents. Therefore, considering that natural products have been an important potential source of new antimicrobial drugs, aim to verify the synergism by disk and time kill curve method between antimicrobials (extracts-Ext. and essential oils-EO) from four plant and eight antimicrobial drugs against Staphylococcus aureus and Escherichia coli strains from human specimens. The S. aures strains were highly susceptible with all plant antimicrobials (eg., 1.24 mg/ml with Vernonia polyanthes Ext. and 2.21 mg/ml with Eugenia uniflora EO for the Minimal Inhibitory Concentration-MIC). According disk method, the Bacharis dracunculifolia and V. polyanthes EO had synergism with all eight tested drugs while only Matricaria chamomilla Ext. showed synergism against S. aureus. The synergism was found with V. polyanthes and E. uniflora Ext. while M. chamomilla Ext. had antagonism against E. coli strains. By time kill curve, the bacterial growth inhibition was superior when drugs were tested alone and the synergism effect also was verified. The antagonism effect was detected only for E. coli strains and only with Ext. Results indicated the potential use of these products as coadjutants during treatment of infectious diseases.

Phenolic compounds influence seed dormancy of palicourea rigida h.b.k. (rubiaceae), a medicinal plant of the brazilian savannah

Palicourea rigida H.B.K. (Rubiaceae), a medicinal species commonly known as douradinha, has wide distribution across ecosystems in Central and South America. This species exhibits seed dormancy delaying germination until optimal conditions for seedling growth and development are in place. While dormancy ensures species survival, it also presents a technical problem for developing P. rigida’s plant production program. Thus, the objective of this study was to investigate if secondary metabolites present in seeds influence the seed dormancy of P. rigida. Mature fruits were harvested from the native habitat, in the savanna region of the State of Minas Gerais during February 2009, 2010 and 2011. The content of phenolic compounds in the seed of P. rigida was measured, and the allelopathic effects were assessed using the germination of lettuces as model to detect phytotoxicity. The P. rigida seeds geminated at rates varying between 7% and 31% with a Seed Germination Index (SGI) of 0.09. Data suggest that the phenolic compounds present in the seeds may be responsible for seed dormancy.

Documentação química de espécies do gênero Casearia (Salicaceae) de importância ecológica, econômica e medicinal

The Casearia genus (Salicaceae) is well known because of the medicinal use of its species. Among them, a noteworthy one is the C. sylvestris specie because it already has studies concerning its antiproliferative and/or cytotoxic activity in tumor cells. Furthermore, this specie is popularly used against snake bites, in gastric ulcers treatment and as anti-inflammatory. As well as this, there are other species from this same genus which have been poorly studied, such as the following species: C. decandra, C. grandiflora, C. javitensis, C. arborea, C. lasiophylla and C. ulmifolia. However, several biological activities have been reported for them. In this context, the aim of this project, besides of contributing to the Casearia genus studies, is to study those six species through the analysis and documentation of their leaves' chemical composition (aqueous, ethanolic and hexanic extracts), using analytical separation techniques coupled with spectroscopic techniques, such as UHPLC-DAD, GC-MS and NMR 1H, which will assist the identification of new secondary metabolites in this genus. Moreover, another goal of this present work is aiming the bioprospection of substances with medicinal and economical potential and finally promote the systematic study of some biological activities, such as antimicrobial and cytotoxicity bioassays. A wide variety of metabolites was identified in those three types of extracts, being most of them detected for the first time in Casearia genus, highlighting C. lasiophylla and C. decandra for featuring antimicrobial activity against Staphylococcus aureus.

Documentação química de espécies do gênero Casearia (Salicaceae) de importância ecológica, econômica e medicinal

The Casearia genus (Salicaceae) is well known because of the medicinal use of its species. Among them, a noteworthy one is the C. sylvestris specie because it already has studies concerning its antiproliferative and/or cytotoxic activity in tumor cells. Furthermore, this specie is popularly used against snake bites, in gastric ulcers treatment and as anti-inflammatory. As well as this, there are other species from this same genus which have been poorly studied, such as the following species: C. decandra, C. grandiflora, C. javitensis, C. arborea, C. lasiophylla and C. ulmifolia. However, several biological activities have been reported for them. In this context, the aim of this project, besides of contributing to the Casearia genus studies, is to study those six species through the analysis and documentation of their leaves' chemical composition (aqueous, ethanolic and hexanic extracts), using analytical separation techniques coupled with spectroscopic techniques, such as UHPLC-DAD, GC-MS and NMR 1H, which will assist the identification of new secondary metabolites in this genus. Moreover, another goal of this present work is aiming the bioprospection of substances with medicinal and economical potential and finally promote the systematic study of some biological activities, such as antimicrobial and cytotoxicity bioassays. A wide variety of metabolites was identified in those three types of extracts, being most of them detected for the first time in Casearia genus, highlighting C. lasiophylla and C. decandra for featuring antimicrobial activity against Staphylococcus aureus.

Enrichment of Pleurotus ostreatus mushrooms with selenium in coffee husks

Pleurotus ostreatus fungus forms an edible mushroom that possesses important nutritional and medicinal properties. Selenium (Se) is essential to human diets and it is in low concentration in the soil, and consequently in food. P. ostreatus was grown in coffee husks enriched with various concentrations of sodium selenite. The biological efficiency of P. ostreatus was affected by the addition of high concentrations of Se. The highest level of Se absorption was obtained by adding 51 mg kg(1) of sodium selenite. The mushrooms from first flush contained more Se than the further flushes. These results demonstrate the great potential of coffee husks in the production of Se-enriched mushrooms and show the ability of this fungus to absorb and biomagnify Se. (C) 2011 Elsevier Ltd. All rights reserved.

In vitro activity of extracts and isolated polyphenols from West African medicinal plants against Plasmodium falciparum

The aim of the study was to screen 11 selected traditional medicinal plants from West Africa for their in vitro antiplasmodial activity in order to determine the activity of single and of combination of plant extracts and to examine the activity of isolated pure compounds. Ethanolic and aqueous extracts of the 11 selected plants and pure compounds from Phyllanthus muellerianus and Anogeissus leiocarpus were tested in vitro against Plasmodium falciparum 3D7. Proliferation inhibitory effects were monitored after 48 h. Among the plants and pure compounds investigated in this study, geraniin from P. muellerianus, ellagic, gentisic, and gallic acids from A. leiocarpus, and extracts from A. leiocarpus, P. muellerianus and combination of A. leiocarpus with P. muellerianus affected the proliferation of P. falciparum most potently. Significant inhibitory activity was observed in combination of A. leiocarpus with P. muellerianus (IC50 = 10.8 mu g/ml), in combination of A. leiocarpus with Khaya senegalensis (IC50 = 12.5 mu g/ml), ellagic acid (IC50 = 2.88 mu M), and geraniin (IC50 = 11.74 mu M). In general growth inhibition was concentration-dependent revealing IC50 values ranging between 10.8 and -40.1 mu g/ml and 2.88 and 11.74 mu M for plant extracts and pure substances respectively. Comparison with literature sources of in vivo and in vitro toxicity data revealed that thresholds are up to two times higher than the determined IC50 values. Thus, the present study suggests that geraniin from P. muellerianus; ellagic acid, gallic acid, and gentisic acid from A. leiocarpus; and combination of extracts from A. leiocarpus with either P. muellerianus or K. senegalensis could be a potential option for malaria treatment.

Cadmium determination in Lentinus edodes mushroom species

Many studies have drawn attention to the occurrence and concentration of toxic elements found in the fruiting body of mushrooms. Some edible mushroom species are known to accumulate high levels of inorganic contaminants, mainly cadmium, mercury, and lead. There are about 2,000 known edible mushroom species, but only 25 of them are cultivated and used as food. In Brazil, the most marketed and consumed mushroom species are Agaricus bisporus, known as Paris champignon, Lentinus edodes, or Shitake and Pleurotus sp, also called Shimeji or Hiratake. In this study, the concentration of cadmium was determined in Lentinus edodes mushrooms from different cities in São Paulo state and some samples imported from Japan and China. The analyses were performed by graphite furnace atomic absorption spectrometry after HNO3-H2O2 digestion. The results showed a lower concentration of Cd in the mushrooms cultivated in São Paulo (0.0079 to 0.023 mg.kg-1 in natura) than that of the mushrooms cultivated abroad (0.125 to 0.212 mg.kg-1 in natura). Although there is no tolerance limit for Cd in mushrooms in Brazil, the results show that Lentinus edodes mushrooms can be safely consumed.

Chemical constituents from three medicinal plants: Piper renitens, Siparuna guianensis and Alternanthera brasiliana

Chemical study of three medicinal plants: from leaves of Piper renitens (Miq.) Yunck, Piperaceae, and Siparuna guianensis Aubl., Siparunaceae, and from flowers of Alternanthera brasiliana (L.) Kuntze, Amaranthaceae, resulted in isolation of nine compounds: three steroids, β-sitosterol, stigmasterol from P. renitens and sitosterol-3-O-β-D-glucopyranoside from A. brasiliana, the diterpene kaurane ent-kauran-16α,17-diol from P. renitens, two derivatives kaempferol-methylether, kumatakenine (kaempferol-3,7-dimethylether) and kaempferol-3,7,3'-trimethylether from S. guianensis and three flavones, crysoeriol (5,7,4'-trihydroxy-3'-methoxyflavone), tricin (5,7,4'-trihydroxy-3',5'-dimethoxyflavone) and 7-O-β-D-glucopyranoside-5,4'-dihydroxy-3'-methoxyflavone from A. brasiliana. Compounds structures were determinate using 1D and 2D ¹H NMR and 13C spectral data, mass and IR spectra, comparing with literature data.

Computational Methods in Biophysics and Medicinal Chemistry: Applications and Challenges

In this thesis I described the theory and application of several computational methods in solving medicinal chemistry and biophysical tasks. I pointed out to the valuable information which could be achieved by means of computer simulations and to the possibility to predict the outcome of traditional experiments. Nowadays, computer represents an invaluable tool for chemists. In particular, the main topics of my research consisted in the development of an automated docking protocol for the voltage-gated hERG potassium channel blockers, and the investigation of the catalytic mechanism of the human peptidyl-prolyl cis-trans isomerase Pin1.

Cancer and aging: a multidisciplinary medicinal chemistry approach on relevant biological targets such as proteasome, sirtuins and interleukin 6

It is well known that ageing and cancer have common origins due to internal and environmental stress and share some common hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury. Moreover, ageing is involved in a number of events responsible for carcinogenesis and cancer development at the molecular, cellular, and tissue levels. Ageing could represent a “blockbuster” market because the target patient group includes potentially every person; at the same time, oncology has become the largest therapeutic area in the pharmaceutical industry in terms of the number of projects, clinical trials and research and development (R&D) spending, but cancer remains one of the leading causes of mortality worldwide. The overall aim of the work presented in this thesis was the rational design of new compounds able to modulate activity of relevant targets involved in cancer and aging-related pathologies, namely proteasome and immunoproteasome, sirtuins and interleukin 6. These three targets play different roles in human cells, but the modulation of its activity using small molecules could have beneficial effects on one or more aging-related diseases and cancer. We identified new moderately active and selective non-peptidic compounds able to inhibit the activity of both standard and immunoproteasome, as well as novel and selective scaffolds that would bind and inhibit SIRT6 selectively and can be used to sensitize tumor cells to commonly used anticancer agents such gemcitabine and olaparib. Moreover, our virtual screening approach led us also to the discovery of new putative modulators of SIRT3 with interesting in-vitro and cellular activity. Although the selectivity and potency of the identified chemical scaffolds are susceptible to be further improved, these compounds can be considered as highly promising leads for the development of future therapeutics.

Channels and transporters. Mini-symposium of the Division of Medicinal Chemistry (DMC) of the Swiss Chemical Society (SCS) at the Department of Chemistry, University of Basel, May 27, 2010

During a half-day symposium, the topic 'Channels and Transporters' was covered with five lectures, including a presentation on 'Introduction and Basics of Channels and Transporters' by Beat Ernst, lectures on structure, function and physiology of channels and transporters ('The Structural Basis for Ion Conduction and Gating in Pentameric Ligand-Gated Ion Channels' by Raimund Dutzler and 'Uptake and Efflux Transporters for Endogenous Substances and for Drugs' by Dietrich Keppler), and a case study lecture on 'Avosentan' by Werner Neidhart. The program was completed by Matthias Hediger who introduced to the audience the National Center of Competence in Research (NCCR)-TransCure in his lecture entitled 'From Transport Physiology to Identification of Therapeutic Targets'.