Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel thiazolidinedione derivative LPSF/RA-4.

A number of studies have demonstrated the biological activities of peroxisome proliferator-activated receptors. However, few studies have addressed the effects of the agonists of these receptors on lung diseases. The aim of the present study was to evaluate the anti-inflammatory action of a novel synthetic thiazolidine derivative (5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/RA-4) on acute lung inflammation (pleurisy) induced by carrageenan.

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients.

Objectives: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients.

Decreased serum interleukin 27 in Brazilian systemic lupus erythematosus patients.

The immunological role of interleukin 27 has been reported in various inflammatory diseases, but its importance in systemic lupus erythematosus pathogenesis is not completely established. The aim of this study was to evaluate serum levels of IL-27 in SLE patients and its correlation with clinical manifestations and disease activity. IL-27 levels were assessed in 70 SLE patients and 30 healthy controls by ELISA.

Cratylia mollis 1, 4 lectin: a new biotechnological tool in IL-6, IL-17A, IL-22, and IL-23 induction and generation of immunological memory.

Cratylia mollis lectin has already established cytokine induction in Th1 and Th2 pathways. Thereby, this study aimed to evaluate Cramoll 1, 4 in IL-6, IL-17A, IL-22, and IL-23 induction as well as analyze immunologic memory mechanism by reinducing lymphocyte stimulation. Initially we performed a screening in cultured splenocytes where Cramoll 1, 4 stimulated IL-6 production 5x more than ConA (P < 0.

The evolution of drugs on schistosoma treatment: looking to the past to improve the future.

Schistosomiasis is a devastating worldwide widespread tropical disease that currently affects more than 230 million people, making it an issue of great socioeconomic and public health importance. Unfortunatelly there is a single drug for the treatment of all forms of schistosomiasis, praziquantel, which was introduced in therapy in 1980. The article goes by antimony compounds, emetine, hydantoin, nitrofurans, lucanthone, hycanthone, oxamniquine derivatives and organophosphates until it finally gets to praziquantel derivatives.

Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives.

Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione - AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione - AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl)-1,3-thiazolidine-2,4-dione - AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2,4-dione - AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner.

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.

Effect of thiazolidine LPSF SF29 on the growth and morphology of Trypanosoma cruzi.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic illness in Latin America. Efforts have been made by several groups to develop new effective and safe anti-T. cruzi drugs.

Photodynamic antimicrobial chemotherapy (PACT) using phenothiazine derivatives as photosensitizers against Leishmania braziliensis.

Background And Objective: Cutaneous and mucocutaneous leishmaniasis are diseases characterized by skin or mucosal manifestations. In the new world, Leishmania braziliensis is the main etiological agent of cutaneous leishmaniasis, condition that may evolve to the mucocutaneous form. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, treatment recommended by the WHO, as they are often highly toxic, poorly tolerated and of variable effectiveness.

Enhanced antiproliferative activity of the new anticancer candidate LPSF/AC04 in cyclodextrin inclusion complexes encapsulated into liposomes.

LPSF/AC04 (5Z)-[5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione] is an acridine-based derivative, part of a series of new anticancer agents synthesized for the purpose of developing more effective and less toxic anticancer drugs. However, the use of LPSF/AC04 is limited due to its low solubility in aqueous solutions. To overcome this problem, we investigated the interaction of LPSF/AC04 with hydroxypropyl-β-cyclodextrin (HP-β-CyD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) in inclusion complexes and determine which of the complexes formed presents the most significant interactions.

New imidazolidine derivatives as anti-Trypanosoma cruzi agents: structure-activity relationships.

Imidazolidine derivatives are key components for the development of bioactive compounds for the treatment of many diseases, especially Chagas. In fact, others studies showed that the imidazolidine-2,4-dione has stood out by presenting a wide spectrum of pharmacological activities including anticonvulsants, antiarrhythmic, and antiparasitic. In the present study, we investigated the morphological alterations induced by imidazolidine derivates LPSF/NN-52 and LPSF/NN-100 on trypomastigotes forms of Trypanosoma cruzi through ultrastructural analysis by electron microscopy.

Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR(-/-)).

Background: Atherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure.

Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis.

A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcus neoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). For antiproliferative activity, the partial least squares (PLS) methodology was applied.

Study of the activity of 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one against Schistosomiasis mansoni in mice.

Previous studies conducted with the imidazolidinic derivative 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin-2-one (LPSF-PT05) show outstanding activity against adult Schistosoma mansoni worms in vitro. In the first phase of this study, S. mansoni-infected mice were treated, orally, with 100 mg/Kg of the LPSF-PT05 in three formulations: Tween 80 and saline solution, oil/water (70 : 30) emulsion, and solid dispersion with polyethylene glycol (PEG).

Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity.

Objective: To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).

Methods: IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables.

GQ-16, a novel peroxisome proliferator-activated receptor γ (PPARγ) ligand, promotes insulin sensitization without weight gain.

The recent discovery that peroxisome proliferator-activated receptor γ (PPARγ) targeted anti-diabetic drugs function by inhibiting Cdk5-mediated phosphorylation of the receptor has provided a new viewpoint to evaluate and perhaps develop improved insulin-sensitizing agents. Herein we report the development of a novel thiazolidinedione that retains similar anti-diabetic efficacy as rosiglitazone in mice yet does not elicit weight gain or edema, common side effects associated with full PPARγ activation. Further characterization of this compound shows GQ-16 to be an effective inhibitor of Cdk5-mediated phosphorylation of PPARγ.

Synthesis and cytotoxic activity of new acridine-thiazolidine derivatives.

Although their exact role in controlling tumour growth and apoptosis in humans remains undefined, acridine and thiazolidine compounds have been shown to act as tumour suppressors in most cancers. Based on this finding, a series of novel hybrid 5-acridin-9-ylmethylene-3-benzyl-thiazolidine-2,4-diones were synthesised via N-alkylation and Michael reaction. The cell viability was analysed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and DNA interaction assays were performed using electrochemical techniques.

Pre-clinical pharmacokinetics of the acridine antitumour candidate AC04 and its 1-oxo-metabolite plasma profile.

This work aimed to investigate plasma pharmacokinetics and tissue distribution of a new acridine derivative 5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) and its 1-oxo-AC04 metabolite disposition in Wistar rats. After a single AC04 1.5 mg/kg intravenous (i.

2-Amino-4,5,6,7-tetra-hydro-benzo[b]thio-phene-3-carbonitrile.

The title compound, C(9)H(10)N(2)S, was synthesized according to Gewald procedures by the reaction of cyclo-hexa-none with malonitrile and sulfur in the presence morpholine. The cyclo-hexane ring adopts a half-chair conformation and the thio-phene ring is essentially planar (r.m.

Anti-inflammatory and antinociceptive activities of indole-imidazolidine derivatives.

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of approximately 50 different medicines that are widely prescribed for the management of inflammation and that exhibit variable anti-inflammatory, anti-pyretic and analgesic activities. Most NSAIDs also exhibit a shared set of adverse effects, particularly related to gastrointestinal complications; thus, the development of new drugs for the treatment of chronic inflammation and pain continues to be an issue of high interest. Hydantoin and indole derivatives are reported to possess various pharmacological effects, including anti-inflammatory and analgesic activities.

Metabolism evaluation of the anticancer candidate AC04 by biomimetic oxidative model and rat liver microsomes.

Jacobsen reagents, in the presence of monooxygen donors, appear as an alternative to produce metabolites from biological active compounds. This reaction may mimic the oxidation and oxygenation reactions of cytochrome P450 (CYP450) enzymes upon various drugs and biologically active compounds. Acridines represent a well-known group of polyaromatic compounds capable of acting as DNA intercalating agents.

Solid dispersions of imidazolidinedione by PEG and PVP polymers with potential antischistosomal activities.

Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to the existence of intermolecular interactions of hydrogen bond type (>N-H···O<) between the amide group (>N-H) of the LPSF/FZ4 and the ether group (-O-) of the polyethyleneglycol polymer, or the carbonyl (C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and thermal analysis of DSC.

Antischistosomal action of thioxo-imidazolidine compounds: an ultrastructural and cytotoxicity study.

Schistosomiasis is a disease caused by helminthes of the genus Schistosoma, which threatens approximately 207 million people worldwide. Recently, strains of Schistosoma mansoni appear to be developing tolerance and resistance against Praziquantel, the most commonly available drug on the market used in the treatment of disease. This worrisome development justifies studies that seek alternatives for the prevention, treatment and cure of this disease.

Development and validation of an HPLC/MS/MS method for determining the thiazolidinone PG15 in rat plasma.

A rapid, sensitive, and simple HPLC/MS/MS method was developed and validated for the determination of (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2, 4-dione (PG15) in rat plasma using chlortalidone as an internal standard (IS). Analyses were performed using a C18 column and isocratic elution with acetonitrile-water (90 + 10, v/v) containing 10 mM ammonium hydroxide (pH 8.0) as the mobile phase pumped at 0.

Synthesis and anti-inflammatory activity of new arylidene-thiazolidine-2,4-diones as PPARgamma ligands.

Eight new 5-arylidene-3-benzyl-thiazolidine-2,4-diones with halide groups on their benzyl rings were synthesized and assayed in vivo to investigate their anti-inflammatory activities. These compounds showed considerable biological efficacy when compared to rosiglitazone, a potent and well-known agonist of PPARgamma, which was used as a reference drug. This suggests that the substituted 5-arylidene and 3-benzylidene groups play important roles in the anti-inflammatory properties of this class of compounds.