Antiparasitic Properties Research Articles

Modulation of cholesterol-related sterols during Eimeria bovis macromeront formation and impact of selected oxysterols on parasite development

Obligate intracellular apicomplexan parasites are considered as deficient in cholesterol biosynthesis and scavenge cholesterol from their host cell in a parasite-specific manner. Compared to fast proliferating apicomplexan species producing low numbers of merozoites per host cell, (e. g. Toxoplasma gondii), the macromeront-forming protozoa Eimeria bovis is in extraordinary need for cholesterol for offspring production (≥ 170,000 merozoites I/macromeront). Interestingly, optimized in vitro E. bovis merozoite I production occurs under low foetal calf serum (FCS, 1.2%) supplementation. To analyze the impact of extensive E. bovis proliferation on host cellular sterol metabolism we here compared the sterol profiles of E. bovis-infected primary endothelial host cells grown under optimized (1.2% FCS) and non-optimized (10% FCS) cell culture conditions. Therefore, several sterols indicating endogenous de novo cholesterol synthesis, cholesterol conversion and sterol uptake (phytosterols) were analyzed via GC–MS-based approaches. Overall, significantly enhanced levels of phytosterols were detected in both FCS conditions indicating infection-triggered sterol uptake from extracellular sources as a major pathway of sterol acquisition. Interestingly, a simultaneous induction of endogenous cholesterol synthesis based on increased levels of distinct cholesterol precursors was only observed in case of optimized parasite proliferation indicating a parasite proliferation-dependent effect. Considering side-chain oxysterols, 25 hydroxycholesterol levels were selectively found increased in E. bovis-infected host cells, while 24 hydroxycholesterol and 27 hydroxycholesterol contents were not significantly altered by infection. Exogenous treatments with 25 hydroxycholesterol, 27 hydroxycholesterol, and 7 ketocholesterol revealed significant adverse effects on E. bovis intracellular development. Thus, the number and size of developing macromeronts and merozoite I production was significantly reduced indicating that these oxysterols bear direct or indirect antiparasitic properties. Overall, the current data indicate parasite-driven changes in the host cellular sterol profile reflecting the huge demand of E. bovis for cholesterol during macromeront formation and its versatility in the acquisition of cholesterol sources.

Leishmanicidal activity of green tea leaves and pomegranate peel extracts on L. infantum

Leishmania infantum is responsible for the cutaneous and visceral form of this zoonotic disease, which is potentially lethal for humans and has dogs as natural reservoir. In the light of the antiparasitic properties displayed by several natural products, L. infantum promastigotes were exposed to green tea (Camellia sinensis) leaves extract (GTE) and pomegranate (Punica granatum) peel extract (PPE). Both extracts, characterized by NMR and HPLC analysis, inhibited parasite proliferation in a dose-dependent manner, as proved by IC50 evaluation determined by MTT assay.Moreover, the reversibility assay showed that GTE and PPE have an aptotosis-mediated leishmanicidal effect, as evidenced by DNA degradation and confirmed by DNA fragmentation and real-time PCR analyses. Finally, for the first time morphological and ultrastructural alterations induced by a P. granatum extract on Leishmania were shown by the use of light, transmission and scanning electron microscopy.

Red and Blue Light Promote the Accumulation of Artemisinin in Artemisia Annua L.

Artemisinin, which has been isolated from Artemisia annua L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in A. annua is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ultraviolet B and C irradiation have been reported to improve the artemisinin content in A. annua, but they are harmful to plant growth and development. Therefore, we screened other light sources to examine if they could promote artemisinin content without affecting plant growth and development. We found that red and blue light could enhance artemisinin accumulation by promoting the expression of the genes that were involved in artemisinin biosynthesis, such as amorpha-4,11-diene synthase (ADS) and cytochrome P450 monooxygenase (CYP71AV1) genes. Thus, in addition to being the main light sources for photosynthesis, red and blue light play a key role in plant secondary metabolism, and optimizing the combination of these light might allow for the productionof artemisinin-rich A. annua.

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.

Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products.

A cultivation-dependent approach revealed that highly diverse populations of Streptomyces were present in atmospheric precipitations from a hailstorm event sampled in February 2016 in the Cantabrian Sea coast, North of Spain. A total of 29 bioactive Streptomyces strains isolated from small samples of hailstone and rainwater, collected from this hailstorm event, were studied here. Taxonomic identification by 16S rRNA sequencing revealed more than 20 different Streptomyces species, with their closest homologs displaying mainly oceanic but also terrestrial origins. Backward trajectory analysis revealed that the air-mass sources of the hailstorm event, with North Western winds, were originated in the Arctic Ocean (West Greenland and North Iceland) and Canada (Labrador), depending on the altitude. After traveling across the North Atlantic Ocean during 4 days the air mass reached Europe and precipitated as hailstone and rain water at the sampling place in Spain. The finding of Streptomyces species able to survive and disperse through the atmosphere increases our knowledge of the biogeography of genus Streptomyces on Earth, and reinforces our previous dispersion model, suggesting a generalized feature for the genus which could have been essential in his evolution. This unique atmospheric-derived Streptomyces collection was screened for production of bioactive secondary metabolites. Analyses of isolates ethyl acetate extracts by LC-UV-MS and further database comparison revealed an extraordinary diversity of bioactive natural products. One hundred molecules were identified, mostly displaying contrasted antibiotic and antitumor/cytotoxic activities, but also antiparasitic, antiviral, anti-inflammatory, neuroprotector, and insecticide properties. More interestingly, 38 molecules not identified in natural products databases might represent new natural products. Our results revealed for the first time an extraordinary diversity of Streptomyces species in the atmosphere able to produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products.

Schistosomicidal, antifibrotic and antioxidant effects of Cucurbita pepo L. seed oil and praziquantel combined treatment for Schistosoma mansoni infection in a mouse model.

Despite the seriousness of schistosomiasis, its treatment depends only on praziquantel (PZQ), which has begun to lose its efficacy against the emergent Schistosoma mansoni-resistant strains. Therefore, the discovery of a novel schistosomicidal drug is an urgent priority. This study was designed to evaluate treatment with Cucurbita pepo L. (pumpkin) seed oil (PSO) alone and combined with PZQ against S. mansoni in experimentally infected mice. The study involved five groups: GI was the normal control; GII was the infected control; GIII was treated with an oral dose of PZQ of 500 mg/kg/day for two successive days, starting in the sixth week post infection; GIV was treated with an oral dose of PSO of 50 mg/kg/day for four weeks, starting in the fourth week post infection; and GV was treated with combined PSO-PZQ. Worm burden, tissue egg load and oogram pattern were estimated, and the ultrastructure alterations were examined. Histopathological examination of granuloma diameters, collagen deposition (Picro Sirius red stain), and angiogenesis (immunohistochemical expression of CD34+) was conducted and serum liver enzymes were measured to assess the liver condition. Moreover, the oxidative stress was evaluated by determining the amounts of malondialdehyde and superoxide dismutase in liver homogenates. The results revealed significant changes in all the assessed parameters with PSO administration. However, PZQ was significantly more effective as an antiparasitic agent, whereas PSO was better in terms of fibrosis and oxidative stress. The most significant results were obtained in group V, which may be attributed to a synergy between PZQ and PSO, with antiparasitic, antioxidant and antifibrotic properties.

Use of Unpalatable Forages by Ruminants: The Influence of Experience with the Biophysical and Social Environment.

Simple SummaryUnpalatable forages, due to either low nutrient content or the presence of toxic compounds, are widespread and represent a challenge for ruminant nutrition, health, and welfare. If we find ways to encourage consumption of unpalatable forages, they could provide at least part of the nutrient requirements of ruminants. Our objective was to synthesize the role of diverse environmental experiences on the use of unpalatable forages by ruminants. Experimental evidence shows that experience can alter both morpho-physiological and psychological (learning) mechanisms to better cope with unpalatable forages, particularly early in life when body functions are more amenable to change. Furthermore, experiential learning provides flexibility in diet selection, which is critical in changing foraging environments. By understanding and applying behavioural principles, it is possible to better devise management plans that optimize the nutrition, health, and welfare of herbivores grazing unpalatable forages throughout their life. In addition, a more uniform use of resources can be achieved from the landscape level down to the individual plant, with consequent benefits to ecosystem integrity and stability.Unpalatable forage resources (low nutrient density, potentially toxic metabolites) are widespread and represent a challenge for ruminant nutrition, health, and welfare. Our objective was to synthesize the role of biophysical and social experience on the use of unpalatable forages by ruminants, and highlight derived behavioural solutions for the well-being of soils, plants, and animals. Environmental experiences early in life modulate gene expression and promote learning, which alters morpho-physiological and psychological mechanisms that modify behavioural responses and change food and habitat selection. In this process, ruminants can become better adapted to the habitat where they are reared. Moreover, experiential learning provides flexibility in diet selection, which is critical for changing foraging environments. Learned associations between unpalatable and palatable foods, if ingested in appropriate amounts, sequence, and close temporal association, induce the development of preference for the former type of food. In this way, a more uniform use of resources can be achieved from the landscape level down to the individual plant, with the associated benefits to ecosystem integrity and stability. Ruminants can also learn the medicinal benefits of ingesting foods with toxins (e.g., condensed tannins and saponins with antiparasitic properties). This knowledge on behavioural processes can be translated into behavioural applications that provide low-cost solutions to many challenges that producers face in managing sustainable livestock production systems.

A Bioactive Trypanosoma cruzi Bromodomain Inhibitor from Chemically Engineered Extracts.

A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interesting antiparasitic properties against the different life cycle stages of T. cruzi.

Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values ~10 μM). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties.

The impact of certain flavourings and preservatives on the survivability of larvae of nematodes of Ruminantia

Annualy, helminthic diseases are one of the causes of economic losses in agriculture. Ruminantia are most often observed to be infected with nematodes of the gastrointestinal tract, including Strongyloides papillosus and the representatives of the Strongylida order. Identifying factors which could cause a decrease in the level of infection of agricultural animals with helminthiases would allow stock-raising facilities to regularly achieve high quality dairy and meat production in sufficient quantity. On the basis of this study, we determined the impact of flavourings and source materials approved for use in and on foods (isoamyl alcohol, isoamyl acetate, raspberry ketone, trilon B, methylparaben) on the survivability of larvae of Strongyloides papillosus and Haemonchus contortus, parasitic nematodes of Ruminantia animals. Among these substances, the lowest efficiency against the nematode larvae was found in isoamyl alcohol, isoamyl acetate and trilon B. A stronger effect was caused by methylparaben (for L3 S. papillosus LD50 = 0.67 ± 0.04%, L1 and L2 S. papillosus – LD50 = 0.0038 ± 0.0008%, L3 H. contortus – LD50 = 0.89 ± 0.15%). Minimum efficient dosage of the solutions was 10 g/l. Significant antihelminthic properties were manifested by raspberry ketone (for L3 S. papillosus LD50 = 1.00 ± 0.72%, L1 and L2 S. papillosus – LD50 = 0.07 ± 0.06%, L3 H. contortus – LD50 = 0.39 ± 0.26%). The results show that there is considerable potential for further studies on the antiparasitic properties of these substances against nematodes in the conditions of farming enterprises and agricultural complexes.

Comparative evaluation of efficacy of oral curcumin gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis

Background: A large number of in vitro and in vivo studies in both animals and humans have reported that curcumin has antioxidant, anti-inflammatory, anti-carcinogenic, anti-microbial and anti-parasitic properties. Curcuma longa is also used externally for inflammation of oral mucosa. To overcome the adverse effects caused by the chemical agents, curcumin is proposed as an alternative for the treatment of gingivitis and periodontitis. Aim: This study aimed to evaluate and compare the role of topical application of oral curcumin gel with scaling and root planing (SRP) on chronic periodontitis. Materials and Methods: In this clinical study, forty participants with mild chronic periodontitis were included. Included participants underwent Phase I therapy, after which they were allocated into two groups (20 each), out of which only one group received curcumin gel for topical application. Plaque index (PI), bleeding on probing measured by sulcus bleeding index, probing pocket depth and clinical attachment level (CAL) were recorded at baseline and at the follow-up after 2 months. Results: Both test and control groups showed statistically significant reduction in PI, sulcular bleeding index, pocket probing depth and CAL. Curcumin gel group showed statistically significant difference compared to the control group with respect to PI (<0.001), sulcular bleeding index (<0.001) and pocket probing depth (0.006). Conclusion: Curcumin as an adjunct to SRP showed higher reduction in plaque accumulation, sulcular bleeding and pocket probing depth as compared to SRP alone.

Evaluation of antiparasitic, anticancer, antimicrobial and hypoglycemic properties of organic extracts from Panamanian mangrove plants

Objective: To investigate 33 organic extracts of mangrove plants for: antiparasitic, anticancer, and antibacterial activities, as well as their ability to inhibit the activity of the α-glucosidase enzyme. Methods: Leaves from all different plant mangrove species located in five mangrove zones of the Pacific coast of Panama were collected according to standard procedures. Qualitative phytochemical analysis of the organic extracts was performed by thin layer chromatography. The antiparasitic activity against Plasmodium falciparum, Trypanosoma cruzi and Leishmania donovani, toxicity against Artemia salina, anticancer activity in MCF-7 cell line, and antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa of all organic extract were investigated according protocols stablished in our institution. Finally, the ability to inhibit the enzymatic activity of α-glucosidase was evaluated by monitoring the hydrolysis of p-nitrophenyl α-D- glucopyranoside. Results: Thirty-three different samples belonging to nine different species of vascular plants with seeds of true mangroves were collected. Triterpenoids, phenolics, and tannins were the main groups of compounds found in the sampled mangroves. Saponins, quinones, and coumarins were found in less than 50% of the samples. Laguncularia racemosa showed moderate activity against Plasmodium falciparum. None of the extracts presented anticancer activity. Rhizophora mangle exhibited potent activity against Staphylococcus aureus and Bacillus subtilis [(90.41±7.33)% and (96.02±6.14)% of inhibition]; Avicennia germinans and Conocarpus erectus had activity against Escherichia coli [(71.17±6.15)% and (60.60±5.13)% of inhibition, respectively]. About 60% of the mangroves showed α-glucosidase inhibitory activity. In particular, extracts from Laguncularia racemosa, Pelliciera rhizophorae, Conocarpus erectus, Mora oleifera, and Tabebuia palustris species showed α-glucosidase inhibitory potential, with IC50 values of (29.45±0.29), (20.60±0.70), (730.06±3.74), (25.59±0.37), and (853.39±5.30) μg/mL, respectively. Conclusions: Panamanian mangroves are mainly a promising potential source of hypoglycemic compounds, specifically α-glucosidase inhibitors. These results highlight the therapeutic virtues of extracts from American mangrove plants.

Role of Herbal Immunomodulators in Control of Coccidiosis Disease

Herbal plants and their derivatives have been utilized since antiquity in the control and managementof poultry coccidiosis. The best known herbal plants in use against coccidiosis are corn, wheat bran, ricebran, polysaccharides, soya bean, barley, oat, extracts of grape seed, Dictamnus dasycarpus Turcz, Pulsatillakoreana, Sinomenium acutum, Ulmus macrocarpa, Dichroafe brifuga and other botanical antioxidantswhich contain many active compounds. These compounds have been found to possess antiprotozoal, anti-parasitic, anti-inflammatory and antioxidant properties. Currently demand and utilization of these aforesaidherbs has increased because these have been proved successful and effective in control of coccidiosis, eco-friendly and economical. The effective potential of these herbals and derivatives to have been reviewedovercome coccidiosis effectively in a better way than other synthetic products against which resistancehas been developed.

Paeoniflorin targets apoptosis and ameliorates fibrosis in murine schistosomiasis mansoni: A novel insight

Schistosomiasis is a chronic helminthic disease causing hepatic fibrosis. Some studies demonstrated direct effect of targeting apoptosis on fibrosis regression. This study is a novel trial of Paeoniflorin (PAE) on S. mansoni induced hepatic fibrosis in murine model compared to Praziquantel (PZQ) evaluating their anti-parasitic and anti-fibrotic properties aiming to discover a new therapy that decrease schistosomiasis morbidity. Thirty two laboratory bred Swiss albino male CD-1 mice were used in this study. The mice were classified into four groups (8 mice each), control healthy, control infected, PZQ treated (300 mg/kg/12 h), PAE treated (50 mg/kg/d) groups. All mice groups were sacrificed 15 weeks post infection for assessment of drugs efficacy by parasitological, histopathological, immunohistochemical and serological studies. Our results showed that PAE improved the parasitological parameters including decrease worm burden, immature, mature eggs and increase dead ones yet, still PZQ had the upper hand in this aspect. However, PAE exceeded PZQ as an anti-fibrotic therapy seemed in marked decrease in hepatic mean granuloma diameter and fibrosis area, besides, marked increase in serum tumor necrosis factor-alpha; TNF-α level, caspase-3 and P53 apoptotic expressions. There was marked decrease in serum IL-13 level, nuclear factor-kappa B; NF-kB, Transforming Growth Factor-Beta1; TGF-β1, Alpha-Smooth Muscle Actin; α-SMA fibrotic expressions. Conclusively, PAE could be an anti schistosomiasis mansoni therapy exceeding PZQ in targeting apoptosis and ameliorating fibrosis. This study provides a perspective for a novel therapeutic approach to prevent liver fibrosis following liver injury due to schistosomiasis mansoni.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phy-tochemicals is based on tradition or word of mouth with few evidence-based studies. Moreo-ver, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become perti-nent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of die-tary phytochemicals are known to inhibit ATP synthase. Structural modifications of phyto-chemicals have been shown to increase the inhibitory potency and extent of inhibition. Site-directed mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can re-sult in selective binding and inhibition of microbial ATP synthase. In this review, the therapeu-tic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective target-ing of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections.

Leishmanicidal and Trypanocidal Activity of Metal Complexes with 1,2,4-Triazolo[1,5-a]pyrimidines: Insights on their Therapeutic Potential against Leishmaniasis and Chagas Disease.

Since their first synthesis back in the early 20th century, 1,2,4-triazolo[1,5- a]pyrimidines have aroused increasing interest in very diverse areas ranging from chemotherapy to agriculture or even photography. Their similarity to purines confers a potential bioactivity and this feature has been wisely exploited for therapeutic use, including antifungal, antipyretic, analgesic, antiinflammatory, antitumoral and antiparasitic properties. In this review, we focus on the compounds that these nitrogen heterocycles form with metal ions and their antiparasitic activity and therapeutic potential against two neglected diseases of tropical prevalence, leishmaniasis and Chagas disease.

Bottlenose dolphins (Tursiops truncatus) do also cast neutrophil extracellular traps against the apicomplexan parasite Neospora caninum.

Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear DNA decorated with histones and cytoplasmic peptides which antiparasitic properties have not previously been investigated in cetaceans. Polymorphonuclear neutrophils (PMN) were isolated from healthy bottlenose dolphins (Tursiops truncatus), and stimulated with Neospora caninum tachyzoites and the NETs-agonist zymosan. In vitro interactions of PMN with the tachyzoites resulted in rapid extrusion of NETs. For the demonstration and quantification of cetacean NETs, extracellular DNA was stained by using either Sytox Orange® or Pico Green®. Scanning electron microscopy (SEM) and fluorescence analyses demonstrated PMN-derived release of NETs upon exposure to tachyzoites of N. caninum. Co-localization studies of N. caninum induced cetacean NETs proved the presence of DNA adorned with histones (H1, H2A/H2B, H3, H4), neutrophil elastase (NE), myeloperoxidase (MPO) and pentraxin (PTX) confirming the molecular properties of mammalian NETosis. Dolphin-derived N. caninum-NETosis were efficiently suppressed by DNase I and diphenyleneiodonium (DPI) treatments. Our results indicate that cetacean-derived NETs represent an ancient, conserved and relevant defense effector mechanism of the host innate immune system against N. caninum and probably other related neozoan parasites circulating in the marine environment.

Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite

While most subunit malaria vaccines provide only limited efficacy, pre-erythrocytic and erythrocytic genetically attenuated parasites (GAP) have been shown to confer complete sterilizing immunity. We recently generated a Plasmodium berghei (PbNK65) parasite that lacks a secreted factor, the histamine releasing factor (HRF) (PbNK65 hrfΔ), and induces in infected mice a self-resolving blood stage infection accompanied by a long lasting immunity. Here, we explore the immunological mechanisms underlying the anti-parasite protective properties of the mutant PbNK65 hrfΔ and demonstrate that in addition to an up-regulation of IL-6 production, CD4+ but not CD8+ T effector lymphocytes are indispensable for the clearance of malaria infection. Maintenance of T cell-associated protection is associated with the reduction in CD4+PD-1+ and CD8+PD-1+ T cell numbers. A higher number of central and effector memory B cells in mutant-infected mice also plays a pivotal role in protection. Importantly, we also demonstrate that prior infection with WT parasites followed by a drug cure does not prevent the induction of PbNK65 hrfΔ-induced protection, suggesting that such protection in humans may be efficient even in individuals that have been infected and who repeatedly received antimalarial drugs.

An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities.

A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole derivatives with antibacterial and antiparasitic properties.

Registration of a High Rhizome and High Curcuminoid Yielding Variety of Turmeric (Curcuma longa L) CIM-Pitamber

Curcuma longa L. (Zingiberaceae), commonly known as turmeric, is not only one of the most popular spices for Indian cuisines, is also one of the most valuable medicinal plants of traditional systems of Indian medicine due to its numerous preventive and curative effects. The pharmaceutical importance of turmeric is due to the presence of linear diarylheptanoidal phenolic molecules that are collectively called as curcuminoids like curcumin, demethoxycurcumin and bisdemethoxycurcumin. These compounds are credited with anti-inflammatory, hypocholesterolemic, anti-oxidant, anti-parasitic, anti-spasmodic, antimicrobial, anti-rheumatic, anti-aging and anti-cancer properties. Extensive R&amp;D efforts made during last eight years at CSIR-CIMAP have resulted in the identification of superior clones that can yield more than 50 tons of rhizomes/ha containing more than 10% content of curcuminoids. One such clone rechristened as CIM-Pitambar has been identified, that can produce 60-65 tons rhizomes/ha containing 12.5% curcuminoids in a relatively short span of 180-190 days. This variety has been developed using the method of cloline breeding approach. Among 130 germplasm accessions/clones collected from different parts of India, single plants/clone selection was performed. This variety is also tolerant to leaf blotch disease of turmeric. This variety provides more than 54% higher rhizomes with 92% more curcuminoids, yielding around 165% more curcuminoids/ha than the cultivar IISR Pratibha, Which is the most commonly cultivated variety in North Indian plains. The introduction of CIM-Pitamber in cultivation will enable farmers to double their yield and profits per unit area, and thus will significantly improve the livelihood of poor farmers.