Bioemulsifier from sponge-associated bacteria reduces staphylococcal biofilm.

Biofilm formation is a major health concern and studies have been pursued to find compounds able to prevent biofilm establishment and remove pre-existing biofilms. While biosurfactants (BS) have been well-known for possessing antibiofilm activities, bioemulsifiers (BE) are still scarcely explored for this purpose. The present study aimed to evaluate the bioemulsifying properties of cell-free supernatants produced by Bacillaceae and Vibrio strains isolated from marine sponges and investigate their antiadhesive and antibiofilm activities against different pathogenic Gram-positive and Gram-negative bacteria.

Green SPIONs as a novel highly selective treatment for leishmaniasis: an in vitro study against intracellular amastigotes.

The main goal of this work was to evaluate the therapeutic potential of green superparamagnetic iron oxide nanoparticles (SPIONs) produced with coconut water for treating cutaneous leishmaniasis caused by . Optical and electron microscopy techniques were used to evaluate the effects on cell proliferation, infectivity percentage, and ultrastructure. SPIONs were internalized by both parasite stages, randomly distributed in the cytosol and located mainly in membrane-bound compartments.

Zinc(II)-Sterol Hydrazone Complex as a Potent Anti- Agent: Synthesis, Characterization, and Insight into Its Mechanism of Antiparasitic Action.

Searching for new alternatives for treating leishmaniasis, we present the synthesis, characterization, and biological evaluation against of the new ZnCl() complex. is 22-hydrazone-imidazoline-2-yl-chol-5-ene-3β-ol, a well-known bioactive molecule functioning as a sterol Δ-sterol methyl transferase (24-SMT) inhibitor. The ZnCl() complex was characterized by infrared, UV-vis, molar conductance measurements, elemental analysis, mass spectrometry, and NMR experiments.

Extracellular Vesicles from Venom Are Diverse in Structure and Protein Composition and Interact with Mammalian Cells.

Snake venoms are complex cocktails of non-toxic and toxic molecules that work synergistically for the envenoming outcome. Alongside the immediate consequences, chronic manifestations and long-term sequelae can occur. Recently, extracellular vesicles (EVs) were found in snake venom.

Benzylamines as highly potent inhibitors of the sterol biosynthesis pathway in Leishmania amazonensis leading to oxidative stress and ultrastructural alterations.

Leishmaniasis is a neglected disease caused by protozoan parasites of the Leishmania genus. Benzylamines are a class of compounds selectively designed to inhibit the squalene synthase (SQS) that catalyzes the first committed reaction on the sterol biosynthesis pathway. Herein, we studied seven new benzylamines (SBC 37-43) against Leishmania amazonensis.

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.

Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites.

Kinetoplast DNA (kDNA) bearing unusual mitochondrion of trypanosomatid parasites offers a new paradigm in chemotherapy modality. Topoisomerase II of Leishmania donovani (LdTopII), a key enzyme associated with kDNA replication, is emerging as a potential drug target. However, mode of action of LdTopII targeted compounds in the parasites at sub-cellular level remains largely unknown.

In vitro antileishmanial activity of ravuconazole, a triazole antifungal drug, as a potential treatment for leishmaniasis.

Objectives: Leishmaniasis, one of the most significant neglected diseases around the world, is caused by protozoan parasites of the Leishmania genus. Nowadays, the available aetiological treatments for leishmaniasis have variable effectiveness and several problems such as serious side effects, toxicity, high cost and an increasing number of resistance cases. Thus, there is an urgent need for safe, oral and cost-effective drugs for leishmaniases.

KH-TFMDI, a novel sirtuin inhibitor, alters the cytoskeleton and mitochondrial metabolism promoting cell death in Leishmania amazonensis.

Treatment of leishmaniasis involves the use of antimonials, miltefosine, amphotericin B or pentamidine. However, the side effects of these drugs and the reports of drug-resistant parasites demonstrate the need for new treatments that are safer and more efficacious. Histone deacetylase inhibitors are a new class of compounds with potential to treat leishmaniasis.

Voacamine alters Leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase IB.

Indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. Here we report for the first time that voacamine, isolated from the plant Tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including Indian strain of Leishmania donovani and Brazilian strains of Leishmania amazonensis and Trypanosoma cruzi. It inhibits the relaxation activity of topoisomerase IB of L.

Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine.

Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise the tomato plant (Solanum lycopersicum L.), which results in fruits with low commercial value. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit the growth of P.

Glycosome turnover in Leishmania major is mediated by autophagy.

Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered.

In vitro activity of the antifungal azoles itraconazole and posaconazole against Leishmania amazonensis.

Leishmaniasis, caused by protozoan parasites of the Leishmania genus, is one of the most prevalent neglected tropical diseases. It is endemic in 98 countries, causing considerable morbidity and mortality. Pentavalent antimonials are the first line of treatment for leishmaniasis except in India.

Biology of human pathogenic trypanosomatids: epidemiology, lifecycle and ultrastructure.

Leishmania and Trypanosoma belong to the Trypanosomatidae family and cause important human infections such as leishmaniasis, Chagas disease, and sleeping sickness. Leishmaniasis, caused by protozoa belonging to Leishmania, affects about 12 million people worldwide and can present different clinical manifestations, i.e.

A novel alkyl phosphocholine-dinitroaniline hybrid molecule exhibits biological activity in vitro against Leishmania amazonensis.

Parasitic protozoa of the Leishmania genus cause leishmaniasis, an important complex of tropical diseases that affect about 12 million people around the world. The drugs used to treat leishmaniasis are pentavalent antimonials, miltefosine, amphotericin B and pentamidine. In the present study, we evaluated the effect of a novel alkyl phosphocholine-dinitroaniline hybrid molecule, TC95, against Leishmania amazonensis promastigotes and intracellular amastigotes.

Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice.

Leishmaniasis is one of the most serious worldwide diseases caused by protozoan parasites of the Leishmania genus, affecting millions of people around the world. All currently available treatments present severe toxic side effects, require long-term compliance, cause serious side effects and are uncomfortable for patients. Leishmania amazonensis, a species endemic to Brazil, causes severe localised or diffuse skin lesions in humans.

Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis.

Amiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC(50) values were 4.

Two squalene synthase inhibitors, E5700 and ER-119884, interfere with cellular proliferation and induce ultrastructural and lipid profile alterations in a Candida tropicalis strain resistant to fluconazole, itraconazole, and amphotericin B.

Three quinuclidine-based squalene synthase (SQS) inhibitors (BPQ-OH, E5700, and ER-119884) were evaluated against five Candida tropicalis strains with different susceptibility profiles to fluconazole (FLC), itraconazole (ITC), terbinafine (TRB), and amphotericin B (AMB). Although the quinuclidine derivatives were inactive against most C. tropicalis strains tested at concentrations up to 16 μg/ml, E5700 and ER-119884 showed antifungal activity against C.

Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis.

Background: Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains.

Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs.

Sterols are constituents of the cellular membranes that are essential for their normal structure and function. In mammalian cells, cholesterol is the main sterol found in the various membranes. However, other sterols predominate in eukaryotic microorganisms such as fungi and protozoa.

Growth inhibition and ultrastructural alterations induced by Delta24(25)-sterol methyltransferase inhibitors in Candida spp. isolates, including non-albicans organisms.

Background: Although Candida species are commensal microorganisms, they can cause many invasive fungal infections. In addition, antifungal resistance can contribute to failure of treatment.The purpose of this study was to evaluate the antifungal activity of inhibitors of Delta24(25)-sterol methyltransferase (24-SMTI), 20-piperidin-2-yl-5alpha-pregnan-3beta-20(R)-diol (AZA), and 24(R,S),25-epiminolanosterol (EIL), against clinical isolates of Candida spp.

In vitro activities of ER-119884 and E5700, two potent squalene synthase inhibitors, against Leishmania amazonensis: antiproliferative, biochemical, and ultrastructural effects.

ER-119884 and E5700, novel arylquinuclidine derivatives developed as cholesterol-lowering agents, were potent in vitro growth inhibitors of both proliferative stages of Leishmania amazonensis, the main causative agent of cutaneous leishmaniasis in South America, with the 50% inhibitory concentrations (IC(50)s) being in the low-nanomolar to subnanomolar range. The compounds were very potent noncompetitive inhibitors of native L. amazonensis squalene synthase (SQS), with inhibition constants also being in the nanomolar to subnanomolar range.

The binding of Tritrichomonas foetus to immobilized laminin-1 and its role in the cytotoxicity exerted by the parasite.

The recognition and binding of pathogens to extracellular matrix glycoproteins may determine the outcome of infective processes. The interaction between the bovine urogenital parasite Tritrichomonas foetus and the major basal membrane glycoprotein laminin-1 (LMN-1) was investigated. The chemical nature of parasite molecules involved in the attachment of T.

Ultrastructural alterations in organelles of parasitic protozoa induced by different classes of metabolic inhibitors.

Parasitic protozoa such as Leishmania, Trypanosoma, Plasmodium, Toxoplasma gondii, Giardia and Trichomonas are able to cause several diseases affecting millions of people around the world with dramatic consequences to the socio-economic life of the affected countries. Diseases like malaria, leishmaniasis and trypanosomiasis have been classified by the World Health Organization as neglected diseases, because they have been almost completely forgotten by the governments as well as the pharmaceutical companies. The specific chemotherapy currently employed for the treatment of these diseases has serious limitations due to lack of efficacy, toxic side effects, growth of drug-resistance and high costs.