Valorizing Constituents of Cashew Nut Shell Liquid toward the Sustainable Development of New Drugs against Chagas Disease.

Six new ether phospholipid analogues encompassing constituents from cashew nut shell liquid as the lipid portion were synthesized in an effort to valorize byproducts of the cashew industry toward the generation of potent compounds against Chagas disease. Anacardic acids, cardanols, and cardols were used as the lipid portions and choline as the polar headgroup. The compounds were evaluated for their antiparasitic activity against different developmental stages of .

Design, synthesis and biological evaluation of antiparasitic dinitroaniline-ether phospholipid hybrids.

A series of nine novel ether phospholipid-dinitroaniline hybrids were synthesized in an effort to deliver more potent antiparasitic agents with improved safety profile compared to miltefosine. The compounds were evaluated for their in vitro antiparasitic activity against L. infantum, L.

Silver and copper-benznidazole derivatives as potential antiparasitic metallodrugs: Synthesis, characterization, and biological evaluation.

Currently the only drug available to treat Chagas disease in Brazil is benznidazole (BZN). Therefore, there is an urgent need to discover and develop new anti- Trypanosoma cruzi candidates. In our continuous effort to enhance clinical antiparasitic drugs using synergistic strategy, BZN was coordinated to silver and copper ions to enhance its effectiveness to treat that illness.

Effects of the natural antimicrobial peptide aureocin A53 on cells of Staphylococcus aureus and Streptococcus agalactiae involved in bovine mastitis in the excised teat model.

Aureocin A53 is an N-formylated antimicrobial peptide (AMP) produced by Staphylococcus aureus. Aureocin A53 has a broad spectrum of antimicrobial activity against human and animal pathogens. In the present study, its antagonistic activity was investigated towards 30 strains of S.

Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids.

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against and intracellular amastigotes, against and against different developmental stages of . The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure-activity relationships.

May the epimastigote form of Trypanosoma cruzi be infective?

For many years it has been considered that there are three basic developmental stages of Trypanosoma cruzi: Epimastigote (Epi), Amastigote (Ama) and Trypomastigote (Typo). Epi and Ama are able to divide while Trypo does not divide. Epi are not infective while Ama and Trypo are able to infect host cells.

Mechanisms of Entry Into Host Cells.

, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite. can invade and multiply inside any nucleated cell of a wide range of homeothermic hosts. The canonical process of internalization involves several steps: an initial recognition of the host cell surface and a sequential secretion of proteins from micronemes followed by rhoptries that assemble a macromolecular complex constituting a specialized and transient moving junction.

Membrane-bound extracellular vesicles secreted by parasitic protozoa: cellular structures involved in the communication between cells.

The focus of this review is a group of structures/organelles collectively known as extracellular vesicles (EVs) that are secreted by most, if not all, cells, varying from mammalian cells to protozoa and even bacteria. They vary in size: some are small (100-200 nm) and others are larger (> 200 nm). In protozoa, however, most of them are small or medium in size (200-400 nm).

Synthesis and Biological Activity of Novel Zinc-Itraconazole Complexes in Protozoan Parasites and spp.

The new complexes Zn(ITZ)Cl (1) and Zn(ITZ)(OH) (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes were characterized by elemental analyses, molar conductivity, mass spectrometry, H and C{H} nuclear magnetic resonance, and UV-vis and infrared spectroscopies. The antiparasitic and antifungal activity of Zn-ITZ complexes was evaluated against three protozoans of medical importance, namely, , , and , and two fungi, namely, and The Zn-ITZ complexes exhibited a broad spectrum of action, with antiparasitic and antifungal activity in low concentrations.

In vitro activities of adamantylidene-substituted alkylphosphocholine TCAN26 against Trypanosoma cruzi: Antiproliferative and ultrastructural effects.

Phospholipids are the main component of membranes and are responsible for cell integrity. Alkylphospholipid analogues (APs) were first designed as antitumoral agents and were later tested against different cell types. Trypanosoma cruzi, the Chagas disease etiological agent, is sensitive to APs (edelfosine, miltefosine and ilmofosine) in vitro.

Clathrin coated pit dependent pathway for Trypanosoma cruzi internalization into host cells.

A number of intracellular pathogens are internalized by host cells via multiple endocytic pathways, including Trypanosoma cruzi, the etiological agent of Chagas disease. Clathrin-mediated endocytosis is the most characterized endocytic pathway in mammalian cells. Its machinery was described as being required in mammalian cells for the internalization of large particles, including pathogenic bacteria, fungi, and large virus.

3D reconstruction of Trypanosoma cruzi-macrophage interaction shows the recruitment of host cell organelles towards parasitophorous vacuoles during its biogenesis.

Trypanosoma cruzi has a complex life cycle where two infective developmental stages, known as trypomastigote and amastigote, can be found in the vertebrate host. Both forms can invade a large variety of cellular types and induce the formation of a parasitophorous vacuole (PV), that, posteriorly, disassembles and releases the parasites into the host cell cytoplasm. The biogenesis of T.

Hyicin 4244, the first sactibiotic described in staphylococci, exhibits an anti-staphylococcal biofilm activity.

Hyicin 4244 is a small antimicrobial peptide with a broad spectrum of activity that was found in the culture supernatant of Staphylococcus hyicus 4244, the genome of which was then sequenced. The bacteriocin gene cluster (hyiSABCDEFG) was mined from its single chromosome and exhibited a genetic organization similar to that of subtilosin A. All genes involved in hyicin 4244 biosynthesis proved to be transcribed and encode proteins that share at least 42% similarity to proteins encoded by the subtilosin A gene cluster.

Nisin and lysostaphin activity against preformed biofilm of Staphylococcus aureus involved in bovine mastitis.

Aims: The biofilm produced by Staphylococcus aureus isolates involved in clinical or subclinical bovine mastitis and the activity of nisin and lysostaphin against the preformed biofilm produced by these strains were investigated.

Methods And Results: Eighteen strains were tested and all produced biofilm. Eight strains with distinct biofilm composition were selected for the antimicrobial activity assays.

Macropinocytosis: a pathway to protozoan infection.

Among the various endocytic mechanisms in mammalian cells, macropinocytosis involves internalization of large amounts of plasma membrane together with extracellular medium, leading to macropinosome formation. These structures are formed when plasma membrane ruffles are assembled after actin filament rearrangement. In dendritic cells, macropinocytosis has been reported to play a role in antigen presentation.

Structures containing galectin-3 are recruited to the parasitophorous vacuole containing Trypanosoma cruzi in mouse peritoneal macrophages.

Trypanosoma cruzi has a complex life cycle where the infective forms for the vertebrate host are trypomastigotes and amastigotes. Both forms invade and lyse their parasitophorous vacuole (PV) membrane, entering into the cytoplasm of its host cells. Galectin-3 (Gal-3) is a protein abundantly distributed in macrophages and epithelial cells.

Trypanosoma cruzi: Entry into Mammalian Host Cells and Parasitophorous Vacuole Formation.

Trypanosoma cruzi, the causative agent of Chagas disease, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are the metacyclic trypomastigotes, amastigotes, and bloodstream trypomastigotes.

Trypanosoma cruzi uses macropinocytosis as an additional entry pathway into mammalian host cell.

Several intracellular pathogens are internalized by host cells via multiple endocytic pathways. It is no different with Trypanosoma cruzi. Evidences indicate that T.

Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi.

The antifungal posaconazole (PCZ) is the most advanced candidate for the treatment of Chagas disease, having potent anti-Trypanosoma cruzi activity in vitro and in animal models of the disease as well as an excellent safety profile in humans. Amiodarone (AMD) is the antiarrhythmic drug most frequently used for the symptomatic treatment of chronic Chagas disease patients, but it also has specific anti-T. cruzi activity.

Review on Trypanosoma cruzi: Host Cell Interaction.

Trypanosoma cruzi, the causative agent of Chagas' disease, which affects a large number of individuals in Central and South America, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are metacyclic and bloodstream trypomastigote and amastigote.

Dynasore, a dynamin inhibitor, inhibits Trypanosoma cruzi entry into peritoneal macrophages.

Background: Trypanosoma cruzi is an intracellular parasite that, like some other intracellular pathogens, targets specific proteins of the host cell vesicular transport machinery, leading to a modulation of host cell processes that results in the generation of unique phagosomes. In mammalian cells, several molecules have been identified that selectively regulate the formation of endocytic transport vesicles and the fusion of such vesicles with appropriate acceptor membranes. Among these, the GTPase dynamin plays an important role in clathrin-mediated endocytosis, and it was recently found that dynamin can participate in a phagocytic process.

Participation of macrophage membrane rafts in Trypanosoma cruzi invasion process.

Membrane rafts are small and dynamic regions enriched in sphingolipids, cholesterol, ganglioside GM1 and protein markers like flotillins, forming the flatter domains or caveolins, which are characterized as stable flask-shape invaginations. We explored whether membrane rafts participate in the entry of Trypanosoma cruzi's trypomastigotes into murine macrophages through transient depletion of macrophage membrane cholesterol with methyl-beta-cyclodextrin and treatment with filipin. These treatments led to a decrease in the trypomastigote invasion process.