Susceptibility of Axenic Amastigotes to the Calpain Inhibitor MDL28170.

Leishmaniasis encompasses a group of neglected diseases caused by flagellated protozoa belonging to the genus, associated with high morbidity and mortality. The search for compounds with anti- activity that exhibit lower toxicity and can overcome the emergence of resistant strains remains a significant goal. In this context, the calpain inhibitor MDL28170 has previously demonstrated deleterious effects against promastigote forms of , which led us to investigate its role on axenic amastigote forms.

Extracellular Vesicles from Mycelial Cells: Implication for Fungal-Host Interplays.

The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus . Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density.

Manganese(II), copper(II) and silver(I) complexes containing 1,10-phenanthroline/1,10-phenanthroline-5,6-dione against species.

New chemotherapeutics are urgently required to treat infections caused by drug-resistant strains. The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different species. Proliferation of , , , , , , , , and was inhibited by three of six Cu(II) (MICs 1.

Chagas Disease Control-Many Approaches to Prospect.

Chagas disease is an emerging and neglected tropical disease caused by the protozoan parasite estimated to infect 8 to 10 million people worldwide, according to the World Health Organization [...

Repurposing Benzimidazoles against Causative Agents of Chromoblastomycosis: Albendazole Has Superior In Vitro Activity Than Mebendazole and Thiabendazole.

Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential.

In Vitro Effects of Aminopyridyl Ligands Complexed to Copper(II) on the Physiology and Interaction Process of .

Chagas disease is derived from the infection by the protozoan . In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu, namely, -aquadichloro(-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper () and its glycosylated ligand -dichloro (-{[4-(2,3,4,6-tetra--acetyl-β-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (), are effective against trypomastigote forms.

Repositioning drug strategy against Trypanosoma cruzi: lessons learned from HIV aspartyl peptidase inhibitors.

Chagas disease (CD) is an old neglected problem that affects more than 6 million people through 21 endemic countries in Latin America. Despite being responsible for more than 12 thousand deaths per year, the disease disposes basically of two drugs for its treatment, the nitroimidazole benznidazole and the nitrofuran nifurtimox. However, these drugs have innumerous limitations that greatly reduce the chances of cure.

Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B.

The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti- activity, therefore its use in association with standard drugs could provide a new alternative for the treatment strategy against leishmaniasis. In this study, we analyzed the potential of the combination of MDL28170 and the antileishmanial drug amphotericin B against and .

Lopinavir and Nelfinavir Induce the Accumulation of Crystalloid Lipid Inclusions within the Reservosomes of and Inhibit Both Aspartyl-Type Peptidase and Cruzipain Activities Detected in These Crucial Organelles.

Several research groups have explored the repositioning of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) on opportunistic infections caused by bacteria, fungi and protozoa. In , HIV-PIs have a high impact on parasite viability, and one of the main alterations promoted by this treatment is the imbalance in the parasite's lipid metabolism. However, the reasons behind this phenomenon are unknown.

In vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine)zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis.

Leishmaniasis is one of the most relevant neglected tropical diseases in the world, affecting 14 million people. Despite the high morbidity, mortality and socio-economic impact, few therapeutic options are available for this disease. To make matters worse, the available molecules have several limitations such as limited efficacy, high cost, side effects and increased resistance.

Biological properties of functional flavoring produced by enzymatic esterification of citronellol and geraniol present in essential oil.

The chemical composition and biological properties of citronella essential oil were modified by enzymatic esterification reaction of the major monoterpenic alcohols with cinnamic acid. The almost complete conversion of geraniol and citronellol present in the citronella () essential oil, into geranyl (99%) and citronellyl (98%) cinnamates was obtained after 48 hours of reaction using a molar ratio of 3:1 (cinnamic acid/alcohol), lipase concentration (Novozym 435) of 15% (w/w) and 70 °C. The esterified oil showed higher antimicrobial activity against bacteria resistant to oxacillin and penicillin and also greater larvicidal activity against larvae compared to unesterified oil.

Naringenin-Functionalized Multi-Walled Carbon Nanotubes: A Potential Approach for Site-Specific Remote-Controlled Anticancer Delivery for the Treatment of Lung Cancer Cells.

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method.

Funding for Chagas Disease: A 10-Year (2009-2018) Survey.

Chagas disease was discovered in 1909 by the Brazilian scientist Carlos Chagas. After more than 110 years, many outcomes have been achieved in all research fields; however, Chagas disease remains a serious public health problem, mainly in Latin America, being one of the most neglected tropical diseases in the world. As a neglected disease, it receives very little financial support.

Environmentally friendly rhamnolipid production for petroleum remediation.

Biosurfactants have potential applications in the remediation of petroleum-contaminated sites. Several strategies can be used to reduce the production costs of these surfactants and make the process more environmentally friendly. In this study, we combined some of these strategies to produce the rhamnolipid-type biosurfactant, including the use of the genetically modified strain Pseudomonas aeruginosa-estA, an industrial coproduct as a carbon source, a simple and low-cost medium, and a simple downstream process.

In vitro effects of the asymmetric peptidomimetic 157, containing l-tartaric acid core and valine/leucine substituents, on Leishmania amazonensis promastigotes and amastigotes.

The current treatments for leishmaniasis bump into several obstacles, including low efficacy, high costs, long monitoring, and several/severe side effects. Consequently, the search for promising compounds is a tangible need. Recently, we reported the anti-Leishmania amazonensis action of asymmetric peptidomimetic compounds containing tartaric acid as core, especially the 157 derivative that contains valine/leucine substituents in its structure.

Synthesis and antimicrobial activity of a phenanthroline-isoniazid hybrid ligand and its Ag and Mn complexes.

Hydrazide ligand, (Z)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)isonicotinohydrazide, 1 forms from a 1:1 Schiff base condensation reaction between isoniazid (INH) and 1,10-phenanthroline-5,6-dione (phendione). Ag and Mn complexes with 1:2 metal:ligand stoichiometry are prepared: [Ag(1)]NO, [Ag(1)]BF and [Mn(1)](NO). Polymeric {[Ag(1)(NO)]} has 1:1 stoichiometry and forms upon infusion of CHCl into a DMSO solution of [Ag(1)]NO.

Repositioning of HIV Aspartyl Peptidase Inhibitors for Combating the Neglected Human Pathogen Trypanosoma cruzi.

Chagas disease, caused by the flagellate parasite Trypanosoma cruzi, is a wellknown neglected tropical disease. This parasitic illness affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. The changes in its epidemiology facilitate co-infection with the Human Immunodeficiency Virus (HIV), making even more difficult the diagnosis and prognosis.

The serine peptidase inhibitor TPCK induces several morphophysiological changes in the opportunistic fungal pathogen Candida parapsilosis sensu stricto.

Candida parapsilosis sensu stricto (C. parapsilosis) has emerged as the second/third commonest Candida species isolated from hospitals worldwide. Candida spp.

Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase.

Objective: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas' disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing.

Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells.

Background: Scedosporium apiospermum is a ubiquitous, emerging and multidrug-resistant fungal pathogen with still rather unknown virulence mechanisms.

Objectives/methods: The cellular basis of the in vitro interaction between fungi and host cells/tissues is the determinant factor for the development of a successful in vivo infection. Herein, we evaluated the interaction of S.

Rutin derivatives obtained by transesterification reactions catalyzed by Novozym 435: Antioxidant properties and absence of toxicity in mammalian cells.

Flavonoids are one of the most important and diversified phenolic groups among products of natural origin. An important property of this metabolite class is the antioxidant action. This study evaluated the antioxidant and cytotoxic activities and oxidative stress of transesterification products of the flavonoid rutin, catalyzed by Novozym® 435.

Primary evidence of the mechanisms of action of HIV aspartyl peptidase inhibitors on Trypanosoma cruzi trypomastigote forms.

The development of HIV aspartyl peptidase inhibitors (HIV-PIs) and their introduction into AIDS therapy preceded a significant decrease in the incidence, morbidity and mortality of relevant protozoan co-infections. However, few data are available about how HIV-PIs act on pathogenic parasites, such as Trypanosoma cruzi, the etiological agent of Chagas disease. Therefore, the aim of the present work was to evaluate different physiological aspects of the treatment of the infective trypomastigote forms of T.

Asymmetric peptidomimetics containing L-tartaric acid core inhibit the aspartyl peptidase activity and growth of Leishmania amazonensis promastigotes.

Aspartyl-type peptidases are promising chemotherapeutic targets in protozoan parasites. In the present work, we identified an aspartyl peptidase activity from the soluble extract of Leishmania amazonensis promastigotes, which cleaved the fluorogenic peptide 7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D-Arg-amide (cathepsin D substrate) under acidic pH conditions at 37°C, showing a KM of 0.58 μM and Vmax of 129.

The potent cell permeable calpain inhibitor MDL28170 affects the interaction of Leishmania amazonensis with macrophages and shows anti-amastigote activity.

Since the discovery of the28 first drugs used in leishmaniasis treatment up to now, the search for compounds with anti-Leishmania activity without toxic effects and able to overcome the emergency of resistant strains remains a major goal to combat this neglected disease. With this in mind, in the present work, we evaluated the effects of the calpain inhibitor MDL28170 on the interaction process of Leishmania amazonensis promastigote forms with murine peritoneal macrophages and on the intracellular amastigotes. Our results showed that the calpain inhibitor MDL28170 at 15 and 30μM significantly reduced the interaction process of promastigotes with macrophages by 16% and 41%, respectively.