Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections.

Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.

Selenium and protozoan parasitic infections: selenocompounds and selenoproteins potential.

The current drug treatments against protozoan parasitic diseases including Chagas, malaria, leishmaniasis, and toxoplasmosis represent good examples of drug resistance mechanisms and have shown diverse side effects. Therefore, the identification of novel therapeutic strategies and drug compounds against such life-threatening diseases is urgent. According to the successful usage of selenium (Se) compounds-based therapy against some diseases, this therapeutic strategy has been recently further underlined against these parasitic diseases by targeting different parasite´s essential pathways. On the other hand, due to the important functions played by parasite selenoproteins in their biology (such as modulating the host immune response), they can be also considered as a novel therapeutic strategy by designing specific inhibitors against these important proteins. In addition, the immunomodulatory potentiality of these compounds to trigger T helper type 1 (Th1) cells and cytokine-mediated immune response for the substantial induction of proinflammatory cytokines, thus, Se, selenoproteins, and parasite selenoproteins could be further investigated to find possible vaccine antigens. Herein, we collect and present the results of some studies regarding Se-based therapy against protozoan parasitic diseases and highlight relevant information and some viewpoints that might be insightful to advance toward more effective studies in the future.

Ethnobotanical and antimicrobial activities of the Gossypium (Cotton) genus: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The Malvaceae family, an important group of plants that have the Gossypium (cotton) genus has been used in folk medicine to treat microbial diseases and symptoms. AIMS OF THE STUDY: This article aims to understand its ethnobotany expression in communities and scientific elucidation of antimicrobial activities of this genus through literature review. MATERIALS AND METHODS: The bibliographic survey was carried out from 1999 to 2019 with keywords combinations such as "Gossypium + ethnobotanical", " Gossypium + medicinal ", "Gossypium + the biological activity" in scientific databases as Pubmed, Scopus, Web of Science, DOAJ, Scielo, Bireme. RESULTS: After data analysis, we found that the Gossypium genus, specifically Gossypium hirsutum, G. barbadense, G. herbaceum, G. arboreum are the species most cited in the treatment of microbial diseases and symptoms in communities all over the world. In light of scientific elucidation of biological activities, the Gossypium genus has been used to treat protozoal, bacterial, fungal, and viral diseases. CONCLUSIONS: The review demonstrated that the Gossypium genus is a promising source of biological activities against microbial diseases, especially in the treatment of protozoal diseases like malaria.

Anti-trichomonad activities of different compounds from foods, marine products, and medicinal plants: a review.

Human trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.

Melaleuca alternifolia (tea tree) oil and its monoterpene constituents in treating protozoan and helminthic infections.

Australian tea tree (Melaleuca alternifolia) oil (TTO) and its monoterpene constituents such as terpinen-4-ol (T4O), 1,8-cineole, limonene, p-cymene, and α-terpinene have been shown to be effective in controlling a wide range of parasitic infections. The anti-parasitic effects of these compounds are mainly due to their anti-histamine and anti-acetylcholinesterase activities as well as their ability to modulate host inflammatory responses. This review attempts to summarize recent advances in the uses of TTO and its 15 major monoterpene constituents in treating parasitic infections in both humans and animals. Activities against parasitic protozoans (Plasmodium falciparum, Leishmania spp., Trypanosoma spp., Acanthamoeba castellanii, Trichomonas vaginalis, Eimeria, and Ichthyophthirius multifiliis), nematodes (Haemonchus contortus and Anisakis simplex), cestode (Echinococcus ortleppi), and monogeneans (Gasterosteus spp. and Dactylogyrus minutus) have been reported, showing good potentials in treating parasitic infections. Further studies are necessary for developing anti-parasite therapies using TTO or its monoterpenes constituents.

Increased Prevalence of Cestode Infection Associated with History of Deworming among Primary School Children in Ethiopia.

Mass deworming of school-aged children with anthelmintics has been recognized as an effective approach for reducing the burden of soil-transmitted helminth (STH) infections. However, the consequences of this intervention on nontargeted parasite populations sharing the same gastrointestinal niche are unclear. We conducted a cross-sectional survey among three primary schools in Sululta town, Ethiopia, to examine the association between students' histories of deworming treatment in the past 6 months and the prevalence of cestode and protozoan infections. An interviewer-led questionnaire administered to parents provided information on sociodemographic factors, and deworming status was ascertained from school records. Stool samples were collected from 525 children for microscopic examination. The independent associations of "any cestode" (positive either for Hymenolepis nana or Taenia spp. eggs) and "any protozoan" (positive either for Giardia lamblia or Entamoeba histolytica/Entamoeba dispar) with history of deworming were examined using logistic regression. Overall, 25.9% of children were infected with at least one intestinal parasite of which H. nana was the most common. In multivariate analyses, deworming in the past 6 months was positively associated with increased odds of both "any protozoan" and "any cestode" infections; the latter reached statistical significance (AOR = 1.83, 95% CI: 0.69-4.86, P = 0.220, AOR = 3.82, 95% CI: 1.17-12.73, P = 0.029, respectively). If this observed association is causal, a greater understanding of interspecies interactions within the gastrointestinal niche may elucidate possible consequences of mass deworming treatments against STHs on coexisting nontargeted parasites.

Antimicrobial activity of leaf extracts and isolated constituents of Croton linearis.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Croton linearis, known as "rosemary", are widely used in folk medicine in Caribbean countries to treat fever and colds (associated to infections). AIM OF THE STUDY: To evaluate the in vitro antimicrobial activity of extracts and fractions derived from C. linearis leaves. MATERIALS AND METHODS: Bioassay-guided fractionation and isolation of compounds from an ethanolic extract of C. linearis, using flash chromatography and semi-preparative HPLC-DAD-MS (High Performance Liquid Chromatography - Diode Array Detection - Mass Spectrometry). Isolated compounds were characterized by MS, 1D- and 2D-NMR (Nuclear Magnetic Resonance) spectroscopy. The microdilution method with resazurin, as well as direct counting with an optical microscope, were used to determine the in vitro antimicrobial activity against bacteria, fungi and parasites. Moreover, the cytotoxicity on human fetal lung fibroblasts (MRC-5) was evaluated. RESULTS: The total extract and chloroform fraction (ClF) showed high activity against protozoa with IC50 values ranging from 1 to 26 µg/mL, but also cytotoxicity on MRC-5 and PMM (Peritoneal Murine Macrophages). Seven compounds were isolated and characterized for first time in this species: the alkaloids laudanidine, laudanosine, reticuline, corydine, glaucine and cularine and the flavonoid glycoside isorhamnetin-3-O-(6″O-p-trans-coumaroyl)-ß-glucopyranoside. Reticuline showed a weak activity against L. infantum (IC50 148.0 ±â€¯1.2 µM), while the flavonoid was active against T. cruzi (IC50 35.6 ±â€¯2.3 µM). CONCLUSIONS: The results show the antiprotozoal potential of the extract and some isolated constituents, which supports the use of this species in Caribbean folk medicine.

Medicinal fungi: a source of antiparasitic secondary metabolites.

Regions with a tropical climate are frequently affected by endemic diseases caused by pathogenic parasites. More than one billion people worldwide are exposed directly to tropical parasites. The literature cites several antiparasitic metabolites obtained from medicinal plants or via synthetic pathways. However, fungi produce a diversity of metabolites that play important biological roles in human well-being. Thus, they are considered a potential source of novel natural agents for exploitation in the pharmaceutical industry. In this brief review article, we will provide an overview of the current situation regarding antiparasitic molecules derived from filamentous fungi, in particular, those which are effective against protozoan parasites, such as Plasmodium, Trypanosoma, and Leishmania, vectors of some neglected tropical diseases. Diseases and parasitic agents are described and classified, and the antiparasitic properties of natural compounds produced by the fungi of the phyla Basidiomycota and Ascomycota are reviewed herein, in order to explore a topic only sparsely addressed in the scientific literature.

Antiprotozoal activity of medicinal plants used by Iquitos-Nauta road communities in Loreto (Peru).

ETHNOPHARMACOLOGICAL RELEVANCE: In the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help identify new antiprotozoal compounds. AIMS OF STUDY: to inventory and validate the use of medicinal plants by rural people of Loreto region. MATERIALS AND METHODS: Rural mestizos were interviewed about traditional medication of parasite infections with medicinal plants. Ethnopharmacological surveys were undertaken in two villages along Iquitos-Nauta road (Loreto region, Peru), namely 13 de Febrero and El Dorado communities. Forty-six plants were collected according to their traditional use for the treatment of parasitic diseases, 50 ethanolic extracts (different parts for some of the plants) were tested in vitro on Plasmodium falciparum (3D7 sensitive strain and W2 chloroquine resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Cytotoxic assessment (HUVEC cells) of the active extracts was performed. Two of the most active plants were submitted to preliminary bioguided fractionation to ascertain and explore their activities. RESULTS: From the initial plants list, 10 were found to be active on P. falciparum, 15 on L. donovani and 2 on the three parasites. The ethanolic extract from Costus curvibracteatus (Costaceae) leaves and Grias neuberthii (Lecythidaceae) bark showed strong in vitro activity on P. falciparum (sensitive and resistant strain) and L. donovani and moderate activity on T. brucei gambiense. CONCLUSIONS: The Amazonian forest communities in Peru represents a source of knowledge on the use of medicinal plants. In this work, several extracts with antiprotozoal activity were identified. This work contributes to validate some traditional uses and opens subsequent investigations on active compounds isolation and identification.

Homeopathic treatment as an alternative prophylactic to minimize bacterial infection and prevent neonatal diarrhea in calves.

Bovine neonatal diarrhea is common due low immunity in newborn calves, poor management (or absence) of sanitary barriers, and other factors. Newborn calves with diarrhea in the first days of life suffer failure to thrive and may die if left untreated. The aim of this study was to evaluate whether prophylactic administration of a homeopathic product (Dia 100®) can control bovine neonatal diarrhea in calves born on a farm with substantial sanitary challenges. We counted total bacteria and protozoan parasites in fecal samples. We measured serum glucose, total protein, globulin, albumin, cholesterol and triglycerides on days 1, 7 and 14 of life. Twenty newborn calves were maintained in individual stalls, and were divided in two groups: ten untreated animals (control) and ten animals treated with Dia 100®. Fecal consistency was evaluated daily. We diagnosed diarrhea in five animals in the treated group, and in all animals from the control group. Infections with Escherichia coli and Giardia duodenalis were identified as the responsible organisms. The E. coli count was low in the treatment group on day 7 of life compared with the control group. Antibiotics were given to eight animals in the control group, and to two animals in the treatment group. On day of life 7, serum levels of total protein and globulins were higher in the control group, but were lower on day 14. Serum levels of glucose and triglycerides were greater in treated animals on days 7 and 14, suggesting that the homeopathic product contributes to improvement of intestinal health and absorption and nutrients. We conclude that Dia 100® controls diarrhea with 50% of efficacy, and reduces antibiotic utilization.

Artemisinin and its derivatives in treating protozoan infections beyond malaria.

Parasitic protozoan diseases continue to rank among the world's greatest global health problems, which are also common among poor populations. Currently available drugs for treatment present drawbacks, urging the need for more effective, safer, and cheaper drugs. Artemisinin (ART) and its derivatives are some of the most important classes of antimalarial agents originally derived from Artemisia annua L. However, besides the outstanding antimalarial and antischistosomal activities, ART and its derivatives also possess activities against other parasitic protozoa. In this paper we review the activities of ART and its derivatives against protozoan parasites in vitro and in vivo, including Leishmania spp., Trypanosoma spp., Toxoplasma gondii, Neospora caninum, Eimeria tenella, Acanthamoeba castellanii, Naegleria fowleri, Cryptosporidium parvum, Giardia lamblia, and Babesia spp. We conclude that ART and its derivatives may be good alternatives for treating other non-malarial protozoan infections in developing countries, although more studies are necessary before they can be applied clinically.

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.

Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp., Trypanosoma spp., and Plasmodium spp.

Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae).

BACKGROUND: Malaria, trypanosomiasis and leishmaniasis have an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. Currently, there is inadequate armory of drugs for the treatment of malaria, trypanosomiasis and leishmaniasis. This underscores the continuing need for the discovery and development of new anti-protozoal drugs. Consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe anti-plasmodial, anti-trypanosomal and anti-leishmanial drugs. METHODS: Bioassay-guided chromatographic fractionation was employed for the isolation and purification of antiprotozoal alkaloids. RESULTS: The methanol extract from the leaves of Annickia kummeriae from Tanzania exhibited a strong anti-plasmodial activity against the multi-drug resistant Plasmodium falciparum K1 strain (IC50 0.12 ± 0.01 µg/ml, selectivity index (SI) of 250, moderate activity against Trypanosoma brucei rhodesiense STIB 900 strain (IC50 2.50 ± 0.19 µg/ml, SI 12) and mild activity against Leishmania donovani axenic MHOM-ET-67/82 strain (IC50 9.25 ± 0.54 µg/ml, SI 3.2). Bioassay-guided chromatographic fractionation led to the isolation of four pure alkaloids, lysicamine (1), trivalvone (2), palmatine (3), jatrorrhizine (4) and two sets of mixtures of jatrorrhizine (4) with columbamine (5) and palmatine (3) with (-)-tetrahydropalmatine (6). The alkaloids showed low cytotoxicity activity (CC50 30 - >90 µg/ml), strong to moderate anti-plasmodial activity (IC50 0.08 ± 0.001 - 2.4 ± 0.642 µg/ml, SI 1.5-1,154), moderate to weak anti-trypanosomal (IC50 2.80 ± 0.001 - 14.3 ± 0.001 µg/ml, SI 2.3-28.1) and anti-leishmanial activity IC50 2.7 ± 0.001 - 20.4 ± 0.003 µg/ml, SI 1.7-15.6). CONCLUSION: The strong anti-plasmodial activity makes these alkaloids good lead structures for drug development programs.

Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs.

Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. In order to identify inhibitors of protozoan NMTs, we chose to screen a diverse subset of the Pfizer corporate collection against Plasmodium falciparum and Leishmania donovani NMTs. Primary screening hits against either enzyme were tested for selectivity over both human NMT isoforms (Hs1 and Hs2) and for broad-spectrum anti-protozoan activity against the NMT from Trypanosoma brucei. Analysis of the screening results has shown that structure-activity relationships (SAR) for Leishmania NMT are divergent from all other NMTs tested, a finding not predicted by sequence similarity calculations, resulting in the identification of four novel series of Leishmania-selective NMT inhibitors. We found a strong overlap between the SARs for Plasmodium NMT and both human NMTs, suggesting that achieving an appropriate selectivity profile will be more challenging. However, we did discover two novel series with selectivity for Plasmodium NMT over the other NMT orthologues in this study, and an additional two structurally distinct series with selectivity over Leishmania NMT. We believe that release of results from this study into the public domain will accelerate the discovery of NMT inhibitors to treat malaria and leishmaniasis. Our screening initiative is another example of how a tripartite partnership involving pharmaceutical industries, academic institutions and governmental/non-governmental organisations such as Medical Research Council and Wellcome Trust can stimulate research for neglected diseases.

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.

Photodynamic inactivation of microbial pathogens: disinfection of water and prevention of water-borne diseases.

Porphyrins have been shown to act as very efficient photosensitizing agents against a broad number of microbial pathogens, including bacteria, fungi, and protozoa. This property has promising applications at a clinical level for the treatment of infectious diseases by photodynamic therapy. Moreover, this technique is also being used to address environmental problems of high significance, such as the decontamination of wastewaters, the disinfection of fish-farming tanks, the protection of animal species (e.g., amphibians and reptiles) that are endangered by pathogens whose life cycle takes place largely in aqueous media, and the control of populations of noxious insects. Such diversified applications take advantage of the availability of a truly large number of porphyrin derivatives with chemical structures that can be tailored to comply with the physical and chemical properties as well as the biological features of several milieus. In addition, the property typical of porphyrins to absorb essentially all of the wavelengths in the sun emission spectrum allows the promotion of processes largely based on natural resources with significant energy savings and low impact on ecosystems.

Biological evaluation of glycosyl-isoindigo derivatives against the pathogenic agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis).

The biological activities of diversely substituted glycosyl-isoindigo derivatives against the causative agents of tropical diseases (malaria, Chagas disease, leishmaniasis and human African trypanosomiasis) are reported. Some of the compounds tested showed interesting activities with good selectivity indices, particularly against Trypanosoma brucei rhodesiense. These results suggested, for the first time, that glycosyl-isoindigo derivatives could be of interest for the discovery of new lead compounds to treat tropical diseases.

Potent antiprotozoal activity of a novel semi-synthetic berberine derivative.

Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds.