The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

A proposal for chemical characterization and quality evaluation of botanical raw materials using glandular trichome microsampling of yacón (Polymnia sonchifolia, Asteraceae), an Andean medicinal plant

A proposal for chemical characterisation and quality evaluation of botanical raw materials by analysing the glandular trichomes from the leaves of two different populations of yacón (Polymnia sonchifolia Poeppig & Endlicher, Asteraceae) is described. This species is an Andean medicinal plant and the tea prepared with their leaves displays hypoglycemic property. The method was based on the glandular trichome microsampling using LC/DAD. Qualitative chromatographic fingerprints of the glands were obtained by isocratic runs and then compared between the two populations, showing the same qualitative profile. The two main metabolites detected in the glands were later isolated from a leaf rinse extract by preparative separation and identified as the melampolides enhydrin and uvedalin. These compounds, subtypes of sesquiterpene lactones, were used as chemical markers. This technique is applicable to other medicinal plants and can be used for the evaluation of the quality of dried material or leaf rinse extracts.

Neste trabalho é descrita uma proposta para a caracterização química e avaliação da qualidade de drogas vegetais através da análise de tricomas glandulares das folhas de duas populações diferentes de yacón (Polymnia sonchifolia Poeppig & Endlicher, Asteraceae). Esta espécie é uma planta medicinal andina e o chá preparado com suas folhas apresenta propriedade hipoglicemiante. O método baseou-se na microamostragem de tricomas glandulares, empregando-se cromatografia líquida de alta eficiência e detecção por arranjo de diodos. As impressões digitais dos cromatogramas das glândulas foram obtidas em sistema isocrático e comparadas entre si, resultado em um mesmo perfil qualitativo para ambas as populações avaliadas. Os dois metabólitos principais encontrados nas glândulas foram isolados através de métodos preparativos a partir de um extrato de lavagem foliar, sendo identificados como enidrina e uvedalina. Estas substâncias, subtipos de lactonas sesquiterpênicas, foram utilizadas como marcadores químicos. Esta técnica é aplicável a outras plantas medicinais e pode ser usada para avaliar a qualidade de materiais secos ou extratos foliares.

Sesquiterpene lactones and a myoinositol from glandular trichomes of Viguiera quinqueremis (Heliantheae; Asteraceae).

The extract of the floral parts of Viguiera quinqueremis afforded, in addition to known compounds, six new sesquiterpene lactones as well as a new myoinositol derivative. All compounds were detected in glandular trichomes which were collected micromechanically from the anther appendages and were analyzed by HPLC. Structure identification was performed by 1H NMR measurements including LC NMR and LC MS experiments.

Diterpenes and synthetic derivatives from Viguiera aspillioides with trypanomicidal activity.

The dichloromethane extract of the tuberous roots of Viguiera aspillioides was tested in vitro against T. cruzi and then investigated in order to identify its active compounds, which were the known diterpenes (-)-ent-kaur-16-en-19-oic acid, (-)-trachyloban-19-oic acid, and (-)-kauran-16alpha-ol. Synthetic derivatives of the acidic compounds were obtained and tested; one of them, (-)-kaur-16-en-19-ol, was also active. Their IC50 are given.

[Gastric neoplasm associated with IgA deficiency. Importance of multidisciplinary care]. / Neoplasia gástrica associada a défice de IgA. Importância da Multidisciplinaridade de Cuidados.

We present the case of 55-year old female patient with a rare malignant disease of the stomach associated with IgA deficiency. For its management the surgical, transfusional and renal support strategy required good coordination of pre, intra and post-operative care, and good articulation among the various sub-specialties. The patient experienced two severe anaphylactoid transfunctional reactions. Congenital IgA deficiency was detected with probable anti-IgA immunization associated with a metacrone adenocarcinoma of the stomach and nephrotic syndrome with renal failure. The transfusion methods utilized are discussed, and the results of the study aimed at detecting a compatible donor, with identical deficit, among family members are presented. In the absence of a national registry of donors with IgA deficiency, the prevention of these potentially dangerous reactions imposes a burden on the Service of Immuno-Hematherapy to take special measures on its own. This case points out the need to implement a blood bank with rare groups and IgA deficient blood, for homo/autologous transfusions.