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[Display omitted] • Planning of new Benzimidazole N- acylhydrazones with antitrypanosomal activity. • Biological evaluation of the compounds against T. cruzi strains (Y and Tulahuen) • Biological evaluation of the compounds against L. amazonensis and L. infantum. In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N -acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)- N '-((5-Nitrofuran-2-yl)methylene)-1 H -benzo[ d ]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC 50 /120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC 50 /120 h = 1.520 μM, SI = 1390). Another compound (E)- N '-(2-Hydroxybenzylidene)-1 H -benzo[ d ]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC 50 /120 h of 3.600 μM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi. [ABSTRACT FROM AUTHOR]

Abstract Visceral Leishmaniasis (VL) is a severe disease, caused by the protozoans Leishmania infantum and L. donovani that is widely diagnosed using serological tools. These, however, have limitations in performance that limit their use for the correct identification of the cases. This study aimed to evaluate the performance of flow cytometry with fixed parasites for VL diagnosis, comparing it with four other serological tests. Samples from two endemic VL regions in Brazil, diagnosed by direct examination (DG1) and by at least two or one standard serological test (DG2 and DG3, respectively), as well as patients with chronic Chagas' disease (CG1) and healthy controls (CG2) were used in this study. The flow cytometry results were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). Using a 1:4096 serum dilution, a ROC curve analysis of the serum titration on flow cytometry has indicated a PPFP of 2% as the cutoff point to segregate positive and negative results. In the present study, flow cytometry had the best performance for DG1 (sensitivity of 96%) while rK39 (imunocromagraphic rapid test) and DAT (Direct agglutination test) were also associated with high sensitivity and specificity. The substantial agreement and kappa indexes observed suggested similar performances between these two tests and flow cytometry. IFAT (Immunofluorescent antibody test) and ELISA (Enzyme-linked immunosorbent assay) had lower performances and the lower values of agreement with flow cytometry. Together, these findings suggest that although adjustments are needed in order to reduce cross reactivity with other trypanosomatids, flow cytometry has the potential to be a safe serological alternative for the diagnosis of VL. Highlights • Flow cytometry may be a safe tool for the diagnosis of patients with Leishmania positive. • The IFAT presented low performance and low concordance with flow cytometry. • Flow cytometry showed high agreement with DAT and rK39 test rapid. [ABSTRACT FROM AUTHOR]

Cancer remains a high incidence and mortality disease, causing around 8.2 million of deaths in the last year. Current chemotherapy needs to be expanded, making research for new drugs a necessary task. Immune system modulation is an emerging concept in cancer cell proliferation control. In fact, there are a number of mechanisms underlying the role immune system plays in tumor cells. In this work, we describe the structural design, synthesis, antitumor and immunomodulatory potential of 31 new 1,3-thiazole and thiosemicarbazone compounds. Cisplatin was used as anticancer drug control. Cytotoxicity against J774A.1 macrophages and antitumor activity against HT-29 and Jurkat cells was determined. These 1,3-thiazole and thiosemicarbazone compounds not only exhibited cytotoxicity in cancer cells, but were able to cause irreversible cancer cell damage by inducing necrosis and apoptosis. In addition, these compounds, especially pyridyl-thiazoles compounds, regulated immune factors such as interleukin 10 and tumor necrosis factor, possible by directing immune system in favor of modulating cancer cell proliferation. By examining their pharmacological activity, we were able to identify new potent and selective anticancer compounds. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82g 5-FU per 1.0g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production. [Copyright &y& Elsevier]

A polypeptide chain formed by recombinant antigens, cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) (CF-Chimera) of Trypanosoma cruzi, was adsorbed on gold and platinum electrodes and investigated by electrochemical impedance spectroscopy on phosphate buffer saline solutions (PBS) containing a redox couple. It was found that the adsorption is strongly sensitive to the oxide layer on the electrode surface. In the majority of the experiments the antigens retained their activity as observed through their interaction with sera from chronic chagasic patients. The results expressed in terms of the charge transfer resistance across the interface, indicate the viability of using the impedance methodology for the development of a biosensor for serological diagnosis of Chagas’ disease. [Copyright &y& Elsevier]

Leishmaniasis, caused by protozoa belonging to the genus Leishmania , is an important public health problem found in >90 countries and with still limited options for treatment. Development of new anti-leishmanial drugs is an urgent need and the identification of new active compounds is a limiting factor that can be accelerated through large scale drug screening. This requires multiple steps and can be expensive and time consuming. Here, we propose an alternative approach for the colorimetric assessment of anti- Leishmania drug activity that can be easily scaled up. L. amazonensis and L. infantum cell lines were generated having the β-galactosidase (β-gal) gene integrated into their chromosomal 18S rRNA (ssu) locus. Both cell lines expressed high levels of β-gal and had their growth easily monitored and quantified colorimetrically. These two cell lines were then evaluated as tools to assess drug susceptibility and their use was validated through in vitro assays with Amphotericin B, which is routinely used against leishmaniasis. β-gal expression was also confirmed through flow-cytometry, another method of phenotypic detection. With these recombinant parasites, an alternative in vitro model of drug screening against cutaneous and visceral leishmaniasis is now available. • An alternative model of drug screening assessment for leishmania is proposed. • Based on L. amazonensis or infantum with high and stable β-galactosidase expression. • Possibility of quantifying promastigotes and intracellular amastigotes in vitro. • Parasites can be used in a simple, fast and accurate screening method. [ABSTRACT FROM AUTHOR]