Exploring Bioinformatics Solutions for Improved Leishmaniasis Diagnostic Tools: A Review.

Significant populations in tropical and sub-tropical locations all over the world are severely impacted by a group of neglected tropical diseases called leishmaniases. This disease is caused by roughly 20 species of the protozoan parasite from the genus. Disease prevention strategies that include early detection, vector control, treatment of affected individuals, and vaccination are all essential.

Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.

Objective: In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.

Methods: Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.

Results: Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5μM, and the other compounds did not demonstrate selectivity for the virus.

In vitro bioevaluation and docking study of dihydrosphingosine and ethambutol analogues against sensitive and multi-drug resistant Mycobacterium tuberculosis.

Tuberculosis remains a major public health problem and one of the top ten causes of death worldwide. The alarming increase in multidrug-resistant and extensively resistant variants (MDR, pre-XDR, and XDR) makes the disease more difficult to treat and control. New drugs that act against MDR/XDR strains are needed for programs to contain this major epidemic.

Chagas disease: Immunology of the disease at a glance.

Chagas disease is an important neglected disease that affects 6-7 million people worldwide. The disease has two phases: acute and chronic, in which there are different clinical symptoms. Controlling the infection depends on innate and acquired immune responses, which are activated during the initial infection and are critical for host survival.

NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats.

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx).

Streptomyces hygroscopicus UFPEDA 3370: A valuable source of the potent cytotoxic agent nigericin and its evaluation against human colorectal cancer cells.

Streptomyces hygroscopicus UFPEDA 3370 was fermented in submerged cultivation and the biomass extract was partitioned, obtaining a fraction purified named EB1. After purification of EB1 fraction, nigericin free acid was obtained and identified. Nigericin presented cytotoxic activity against several cancer cell lines, being most active against HL-60 (human leukemia) and HCT-116 (human colon carcinoma) cell lines, presenting IC and (IS) values: 0.

Immunogenicity of Potential CD4 and CD8 T Cell Epitopes Derived From the Proteome of .

A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from the proteome of , which were selected by their affinity to MHC complexes. Comparative cell proliferation assays were performed by culturing, in the presence of each peptide, PBMC cells from subclinical subjects (SC), cutaneous leishmaniasis patients with active disease (AD), post-treatment (PT) individuals, and healthy controls.

Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds and were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC values of 13.

A docking-based structural analysis of geldanamycin-derived inhibitor binding to human or Leishmania Hsp90.

Leishmaniasis is a neglected disease that affects millions of individuals around the world. Regardless of clinical form, treatment is based primarily on the use of pentavalent antimonials. However, such treatments are prolonged and present intense side effects, which lead to patient abandonment in many cases.

Anti-hypersensitivity effects of the phthalimide derivative N-(4methyl-phenyl)-4-methylphthalimide in different pain models in mice.

The treatment of chronic pain remains a challenge for clinicians worldwide, independent of its pathogenesis. It motivates several studies attempting to discover strategies to treat the disease. The in silico analysis using molecular docking approach demonstrated that the phthalimide N-(4methyl-phenyl)-4-methylphthalimide (MPMPH-1) presented high affinity to adenylyl-cyclase enzyme (AC).

Supramolecular interactions between β-lapachone with cyclodextrins studied using isothermal titration calorimetry and molecular modeling.

Supramolecular interactions between β-lapachone (β-lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X-ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT-IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed β-, HP-β-, SBE-β-, γ-, and HP-γ-CDs at 1.

Combination of In Silico Methods in the Search for Potential CD4(+) and CD8(+) T Cell Epitopes in the Proteome of Leishmania braziliensis.

The leishmaniases are neglected tropical diseases widespread throughout the globe, which are caused by protozoans from the genus Leishmania and are transmitted by infected phlebotomine flies. The development of a safe and effective vaccine against these diseases has been seen as the best alternative to control and reduce the number of cases. To support vaccine development, this work has applied an in silico approach to search for high potential peptide epitopes able to bind to different major histocompatibility complex Class I and Class II (MHC I and MHC II) molecules from different human populations.

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique.

New 1,3-thiazole derivatives and their biological and ultrastructural effects on Trypanosoma cruzi.

In previous studies, the compound 3-(bromopropiophenone) thiosemicarbazone was described as a potent anti-Trypanosoma cruzi and cruzain inhibitor. In view to optimize this activity, 1,3-thiazole core was used as building-block strategy to access new lead generation of anti T. cruzi agents.

Thiosemicarbazones as Aedes aegypti larvicidal.

A set of aryl- and phenoxymethyl-(thio)semicarbazones were synthetized, characterized and biologically evaluated against the larvae of Aedes aegypti (A. aegypti), the vector responsible for diseases like Dengue and Yellow Fever. (Q)SAR studies were useful for predicting the activities of the compounds not included to create the QSAR model as well as to predict the features of a new compound with improved activity.

Design, synthesis and structure-activity relationship of phthalimides endowed with dual antiproliferative and immunomodulatory activities.

The present work reports the synthesis and evaluation of the antitumour and immunomodulatory properties of new phthalimides derivatives designed to explore molecular hybridization and bioisosterism approaches between thalidomide, thiosemicarbazone, thiazolidinone and thiazole series. Twenty-seven new molecules were assessed for their immunosuppressive effect toward TNFα, IFNγ, IL-2 and IL-6 production and antiproliferative activity. The best activity profile was observed for the (6a-f) series, which presents phthalyl and thiazolidinone groups.

2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: structural design, synthesis and pharmacological evaluation.

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3-thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors and showed excellent inhibition on the trypomastigote form of the parasite, and the resulting structure-activity relationships are discussed. Together, these data present a novel series of thiazolyl hydrazones with potential effects against Chagas disease and they could be important leads in continuing development against Chagas disease.

Structural design, synthesis and structure-activity relationships of thiazolidinones with enhanced anti-Trypanosoma cruzi activity.

Pharmacological treatment of Chagas disease is based on benznidazole, which displays poor efficacy when administered during the chronic phase of infection. Therefore, the development of new therapeutic options is needed. This study reports on the structural design and synthesis of a new class of anti-Trypanosoma cruzi thiazolidinones (4 a-p).

Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus).

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated.

Sulfonamide-metal complexes endowed with potent anti-Trypanosoma cruzi activity.

In this article, we describe that mononuclear complexes composed of (5-chloro-2-hydroxybenzylidene)aminobenzenesulfonamides (L1-3) of general formula (L2(M)2H2O, where M is Co, Cu, Zn, Ni or Mn) reduced epimastigote proliferation and were found cidal for trypomastigotes of Trypanosoma cruzi Y strain. Complexes C5 and C11 have IC50 of 2.7 ± 0.

Chemical synthesis, docking studies and biological effects of a pan peroxisome proliferator-activated receptor agonist and cyclooxygenase inhibitor.

The compound (5Z)-5-[(5-bromo-1H-indol-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione (LYSO-7) was synthesised in order to obtain a new type of anti-inflammatory drug, designed with hybrid features to inhibit cyclooxygenase (COX) and also to activate peroxisome proliferator-activated receptor (PPAR). Results obtained from docking (in silico) studies corroborated with experimental data, showing the potential affinity between the studied ligand and targets. The specificity of LYSO-7 for COX-enzymes was detected by the inhibition of COX-1 and COX-2 activities by 30% and 20%, respectively.