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 ± 0.27 and 4.8 ± 0.47 µM, respectively, for trypomastigotes, when the positive control Nifurtimox, which is also an approved drug for Chagas disease, showed IC50 of 2.7 ± 0.25 µM. We tested whether these complexes inhibit the enzyme T. cruzi trypanothione reductase or acting as DNA binders. While none of these complexes inhibited trypanothione reductase, we observed some degree of DNA binding, albeit less pronounced than observed for cisplatin in this assay. Unfortunately, most of these complexes were also toxic for mouse splenocytes. Along with the present studies, we discuss a number of interesting structure-activity relationships and chemical features for these metal complexes, including computational calculations.

Evaluation of antioxidant, immunomodulatory, and cytotoxic action of fractions from Eugenia uniflora L. and Eugenia malaccensis L.: correlation with polyphenol and flavanoid content.

An increasing number of biological activities presented by medicinal plants has been investigated over the years, and they are used in the search for new substances with lower side effects. Eugenia uniflora L. and Eugenia malaccensis L. (Myrtaceae) have many folk uses in various countries. This current study was designed to quantify the polyphenols and flavonoids contents and evaluate the immunomodulatory, antioxidant, and cytotoxic potentials of fractions from E. uniflora L. and E. malaccensis L. It was observed that the polyphenol content was higher in ethyl acetate fractions. These fractions have high antioxidant potential. E. malaccensis L. seeds showed the largest DPPH radical scavenger capacity (EC50 = 22.62). The fractions of E. malaccensis L. leaves showed lower antioxidant capacity. The samples did not alter the profile of proinflammatory cytokines and nitric oxide release. The results indicate that species of the family Myrtaceae are rich in compounds with antioxidant capacity, which can help reduce the inflammatory response.

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). In the second phase, three other doses of the LPSF-PT05 in PEG were tested: 3, 10, 30 mg/kg. These treatment regimens significantly reduced the number of recovered worms due to increases in the solubility of the compound in this formulation; the greatest reduction (70.5%) was observed at the dose of 100 mg/kg. There was no changes in the pattern of mature egg compared to immature eggs; however there was a significant increase in the number of dead eggs. Histopathological analysis of liver tissue showed changes in morphological aspects of the hepatic parenchyma with decrease exudative-productive hepatic granuloma stages, although we found no significant differences in IFN-γ, IL-4, IL-10, or NO production in response to the specific antigen SEA. The results show the derivative LPSF-PT05 to be a potential candidate in the etiological treatment of schistosomiasis with a possible dampening effect of the granulomatous process.

Biological and immunological activity of new imidazolidines against adult worms of Schistosoma mansoni.

The only drug available for treating schistosomiasis is praziquantel, however there are already reports of resistance to its use in treatment, making it necessary to search and develop new compounds to combat schistosomiasis. We tested, in vitro, two new products, Laboratório de Planejamento de Síntese de Fármacos (LPSF)/5-(4-chloro-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-2) and LPSF/5-(4-fluoride-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-5) imidazolidines, against adult worms of Schistosoma mansoni. Efficacy and safety of these compounds were analyzed through IC50 cytotoxicity, immune response and cell viability tests. At different concentrations ranging from 40-640 microM, the imidazolidines produced motor abnormalities, inhibition of pairing and oviposition and mortality within 24 h at the higher concentrations. Although not triggering changes in IFN-gamma and IL-10, LPSF/RZS-2 and LPSF/RZS-5 induced production of nitric oxide and showed similar behavior to praziquantel in the cell death test.

Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis.

Host immune response against Mycobacterium tuberculosis is mediated by cellular immunity, in which cytokines and Th1 cells play a critical role. In the process of control of the infection by mycobacteria, TNF-alpha seems to have a primordial function. This cytokine acts in synergy with IFN-gamma, stimulating the production of reactive nitrogen intermediates (RNIs), thus mediating the tuberculostatic function of macrophages, and also stimulating the migration of immune cells to the infection site, contributing to granuloma formation, which controls the disease progression. IFN-gamma is the main cytokine involved in the immune response against mycobacteria, and its major function is the activation of macrophages, allowing them to exert its microbicidal role functions. Different from TNF-alpha and IFN-gamma, IL-10 is considered primarily an inhibitory cytokine, important to an adequate balance between inflammatory and immunopathologic responses. The increase in IL-10 levels seems to support the survival of mycobacteria in the host. Although there is not yet conclusive studies concerning a clear dichotomy between Th1 and Th2 responses, involving protective immunity and susceptibility to the disease, respectively, we can suggest that the knowledge about this responses based on the prevailing cytokine profile can help to elucidate the immune response related to the protection against M. tuberculosis.