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The present research aimed at the synthesis of two new systems containing glibenclamide (GLIB) and double layered hydroxides (LDH). GLIB is an important drug used in the treatment of diabetes mellitus II (DM-II). The choice of zinc LDH (Zn2Al-Cl-GLIB) and magnesium (Mg2Al-Cl-GLIB) was performed with a possible antioxidant action, important for the treatment of DM II. The systems were characterized by x-ray diffractometry, medium infrared spectroscopy, surface area, thermogravimetry and differential exploratory analysis, mass analysis, chemical analyzes of carbon, nitrogen, and hydrogen (CHN) and metals (ICP-OES). The amount of GLIB carried by Mg2Al-Cl-GLIB was 0.625 mMol·g−1 and 0.666 mMol·g−1 by Zn2Al-Cl-GLIB. The release was performed by the dissolution test in simulated gastric and intestinal media. In the intestinal simulated medium LDH Zn2Al-Cl-GLIB and Mg2Al-Cl-GLIB showed a 13% and 30% solubility enhancement in relation to the isolated drug (GLIB), respectively. In addition, Zn2Al-Cl-GLIB presented antioxidant activity, suggesting potential action against free radicals produced in the chronic phase of DM-II. For both systems mesopore formation and absence of cellular toxicity were observed in macrophages.

Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 10(4) to 6.01 × 10(4) M(-1). UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.

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. Forty mice were randomly allocated to the following groups: (I) saline control group (sham); (II) carrageenan (CAR) group; (III) CAR+LPSF/RA-4 group treated with LPSF/RA-4 (60 μmol/kg); and (IV) INDO group treated with indometacin (5mg/kg). Total cell counts and the measure of nitric oxide (NO) were performed in pleural exudates. Lung fragments were processed for light microscopy, transmission electron microscopy, immunohistochemistry and Western blotting. The influx of leucocytes and NO levels were significantly reduced following treatment with LPSF/RA-4 and INDO. Histopathological and ultrastructural analyses of the CAR group revealed evident tissue alterations, such as oedema, infiltrates of inflammatory cells and emphysema. These alterations were significantly reduced in the groups treated with LPSF/RA-4 or INDO. Immunohistochemistry revealed an increase in inflammatory markers (COX-2, iNOS, TNF-α and IL-1β) in the lung tissue of the CAR group, whereas the groups treated with LPSF/RA-4 and INDO exhibited significant reductions in such immunomarkers. Western blot analysis revealed an increased expression of COX-2 and IL-1 in the CAR group, which was reduced by treatment with LPSF/RA-4. The present findings demonstrate the potent anti-inflammatory action of the novel derivative thiazolidinedione LPSF/RA-4 in acute lung injury induced by carrageenan.

A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a “one pot” condensation reaction to α-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide. Most of the compounds effectively suppressed nitric oxide production in murine cells stimulated with lipopolysaccharide. N-phthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-α and IL-1β production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity. [The pharmacological evaluation of eight N-phthaloyl amino acids 2a–h, including their anti-inflammatory and cytotoxic effects and nitric oxide, TNF-α, and IL-1β production, is described.]

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. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways.

One of the most promising areas for the development of functional foods lies in the development of effective methods to reduce or eliminate food allergenicity, but few reports have summarized information concerning the progress made with food irradiation. In this study, we investigated the relationship between allergenicity and molecular structure of a food allergen after gamma irradiation and evaluate the profile of the allergic response to irradiated allergens. Cramoll, a lectin isolated from a bean and used as a food allergen, was irradiated and the possible structural changes were accompanied by spectrofluorimetry, circular dichroism and microcalorimetry. Subsequently, sensitized animals subjected to intragastric administration of non-irradiated and irradiated Cramoll were treated for 7 days. Then, body weight, leukocytes, cytokine profiles and histological parameters were also determined. Cramoll showed complete inhibition of intrinsic activity after high radiation doses. Changes in fluorescence and CD spectra with a simultaneous collapse of the tertiary structure followed by a pronounced decrease of native secondary structure were observed after irradiation. After oral challenge, sensitized mice demonstrate an association between Cramoll intake, body weight loss, eosinophilia, lymphocytic infiltrate in the gut and Eotaxin secretion. Irradiation significantly reduces, according to the dose, the effects observed by non-irradiated food allergens. We confirm that high-dose radiation may render protein food allergens innocuous by irreversibly compromising their molecular structure.

A series of arylamidines 3a-j was designed, synthesized and investigated for antimicrobial activity. Structures of the compounds were confirmed by IR, 1H-NMR and 13C-NMR and a 2D spectroscopic study was performed. A preliminary screening of the antimicrobial tests clearly showed that three out of ten arylamidines, viz, 3f, 3g and 3i, were effective against all the gram-negative bacteria: Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enteric; and against the yeast, candida albicans. Further, the Minimum Inhibitory Concentrations (MIC) against the bacteria and yeast were determined. All compounds 3a-d, 3f, 3g, 3i and 3j were also investigated for their low cytotoxic effects on tested cell lines. Compounds 3d and 3f were the most effective derivatives against HL-60 and HEp-2 cells, respectively, with IC50 value (2µg/mL), and low normal cells toxicity.

Actinomycetes are known to produce numerous secondary bioactive metabolites of pharmaceutical interest. The purpose of this study was to isolate, characterize, and investigate the antibacterial, antifungal, and anticancer activities of metabolites produced by Actinobacteria isolated from the rhizosphere of Paullinia cupana. The Actinobacteria was identified as Streptomyces hygroscopicus ACTMS-9H. Based on a bioguided study, the methanolic biomass extract obtained from submerged cultivation had the most potent antibacterial, antifungal, and cytotoxic activities. This extract was partitioned with n-hexane, ethyl acetate, and 2-butanol. Elaiophylin was isolated from the methanolic biomass extract, and its molecular formula was determined (C54H88O18) based on 1H and 13C NMR, IR and MS analyses. The 2-butanol phase was fractionated into four fractions (EB1, EB2A, EB2B, and EB3M). Chemical prospecting indicated the presence of alkaloids, saponins, and reducing sugars in the methanolic extract and 2-butanol phase. The elaiophylin displayed anticancer activity in HEp-2 and HL-60 cells with an IC50 of 1 μg/mL. The EB1 fraction was selectively toxic to HL-60 cells with IC50 of 9 ng/mL. Bioautography showed that the EB1 fraction contained an alkaloid with antibacterial and antifungal activities (MIC values ≤1.9 and

An efficient approach for the synthesis of Z-1,3-enynes based on the coupling reaction of Z-vinyl tellurides and alkynes containing a pseudoglycoside moiety is described. The products were obtained in good yields via a stereoselective way. Preliminary screening against three tumor cell lines indicated that the synthesized compounds are promising intermediates for the synthesis of an array of more potent target structures.

The present study aimed to evaluate the antimicrobial activity and cytotoxicity of colloidal chitosan - silver nanoparticle - fluoride nanocomposites (CChAgNpFNc), with different silver nanoparticle shapes and sizes. The syntheses of CChAgNpFNc were performed with silver nitrate added to a chitosan solution, addition of a sodium borohydride solution and solid sodium fluoride. Solution of ascorbic acid was added to synthesize larger silver nanoparticles. CChAgNpFNc obtained: S1- 100% spherical, 8.7±3.1nm; S2- 97% spherical, 15.0±7.9nm and 2.5% triangular, 22.2±9.5nm; S3- 77.3% spherical, 31.8±10.4nm, 15.9% triangular, 27.1±10.1nm and 6.8% elliptical, 33.2±7.8nm; and S4- 75.2% spherical, 43.2±14.3nm; 23.3% triangular 38.2±14.8nm, and 1.5% elliptical 38.4±11.6nm. The CChAgNpFNc showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans, by microdilution technique. The influence on the growth of microorganisms was evaluated using a fluorescence assay, and showed an increasing lag phase and a decreasing log phase. Cytotoxicity was investigated using Artemia salina and MTT assays. The S3 and S4 samples exhibited low cytotoxicity. The S1 and S2 samples inhibited murine macrophages and revealed lethal dose concentrations above 1000mg/mL that were classified as moderately toxic. Thus, CChAgNpFNc are potential options for the control of multiple-drug-resistant microorganisms and do not represent substantial risks to human health.

The search for natural products and related analogs as potential anticancer agents has seen a significant growth worldwide. Since small sized propargylic diols can be found in nature and chemically synthesized, their evaluation against cancer cells has been of great interest, being a topic of relevance to be investigated. For this purpose, a scalable approach aiming at the synthesis of several propargylic diols and their bioactivity against seven tumor cell lines were evaluated. Interestingly, when the compound 1a, a natural product produced by fungus Clitocybe catinus, was tested in its racemic mixture a more effective activity was observed if compared when enantiopure R-1a or S-1a were tested separately.

A novel series of twenty 3-thiocyanato-1H-indoles, carrying diversification at positions N-1, C-2 and C-5 of the heterocyclic core, were synthesized; their antiproliferative activity against four human cancer cell lines (HL60, HEP-2, NCI-H292 and MCF-7) was evaluated, employing doxorubicin as positive control. Indole, N-methylindole and 2-(4-chlorophenyl)-N-methylindole demonstrated to be essentially inactive, whereas several of their congener 3-thiocyanato-1H-indoles displayed good to excellent levels of potency (IC50 ≤ 6 μM), while being non-hemolytic. N-Phenyl-3-thiocyanato-1H-indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1H-indole showed good to high potency against all the cell lines. On the other side, the N-(4-chlorophenyl)-, 2-(4-chlorophenyl)- and 2-phenyl- 3-thiocyanato-1H-indole derivatives were slightly less active against the test cell lines. Overall, these results suggest that the indole-3-thiocyanate motif can be suitably decorated to afford highly cytotoxic compounds and that the substituted indole can be employed as a useful scaffold toward more potent compounds. Fil: Fortes, Margiani P.. Universidade Federal de Santa Maria; Brasil Fil: da Silva, Paulo B. N.. Universidade Federal de Pernambuco; Brasil Fil: Da Silva, Teresinha G.. Universidade Federal de Pernambuco; Brasil Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Militão, Gardenia C. G.. Universidade Federal de Pernambuco; Brasil Fil: Silveira, Claudio C.. Universidade Federal de Santa Maria; Brasil

Background: Lichen compounds exhibit remarkable biological activity. Several of them are potent anticancer agent and some with low or none toxicity. The aim of this study was perform in vitro and in vivo assessments of the antineoplastic activity of organic extract and barbatic acid (BAR) isolated from the lichen Cladia aggregata (Sw.) Nyl. Methods: In vitro assays were performed with both extract and BAR against HEp-2 (Adenocarcinoma of the Larynx), NCI-H292 (Squamous Cell Lung Carcinoma) and KB (Nasopharyngeal Squamous Cell Carcinoma) cells. The tests were carried out on the Sarcoma-180 BAR, tumor and organs were analyzed histopatologically after 7 days of chemotherapy. Results: Cytotoxic tests with BAR revealed 50% inhibitory concentration (IC 50 ) of 19.06 µg mL -1 for NCI-H292 and 12.0 µg mL -1 for KB and 6.25 µg mL -1 for HEp-2 cells. Tests with Sarcoma-180 demonstrated 46.3% inhibitory activity against the tumor by BAR. This substance showed no significant effect on the expression of argyrophilic nucleolar organizer regions proteins (AgNORs). The histopathology study of neoplastic tissue, demonstrated that cell proliferation was not affected by the antineoplastic action of the compound tested. Conclusions: The results indicate that barbatic acid exhibits significant antineoplastic activity and low toxicity rate.

The purpose of this study was to evaluate the anti-inflammatory and anti-arthritic activities of 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (β-lapachone; β-lap) and to elucidate its probable mode of action.Carrageenan-induced paw edema, cell migration evaluation and production of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide were used for this study. Freund's complete adjuvant (FCA)-induced arthritis was used as a model of chronic inflammation. β-Lap was tested in doses of 40 and 60 mg/kg, orally.In the paw edema test, the dose of 60 mg/kg gave a higher percentage inhibition of edema (49.3 %) than control. β-Lap inhibited neutrophil migration and reduced concentrations of TNF-α, IL-6 and NO in peritoneal exudates of animals with peritonitis. In the arthritis test, β-lap inhibited edema and NO production in the serum of treated animals.Significant anti-inflammatory and anti-arthritic activities were observed in animals treated with β-lap. The effects of β-lap can be attributed in part to immunomodulation with reduction of pro-inflammatory cytokines and NO.

Trachylobane-360 (ent-7α-acetoxytrachyloban-18-oic acid) was isolated from Xylopia langsdorffiana. Studies have shown that it has weak cytotoxic activity against tumor and non-tumor cells. This study investigated the in vitro and in vivo antitumor effects of trachylobane-360, as well as its cytotoxicity in mouse erythrocytes. In order to evaluate the in vivo toxicological aspects related to trachylobane-360 administration, hematological, biochemical and histopathological analyses of the treated animals were performed. The compound exhibited a concentration-dependent effect in inducing hemolysis with HC50 of 273.6 µM, and a moderate in vitro concentration-dependent inhibitory effect on the proliferation of sarcoma 180 cells with IC50 values of 150.8 µM and 150.4 µM, evaluated by the trypan blue exclusion test and MTT reduction assay, respectively. The in vivo inhibition rates of sarcoma 180 tumor development were 45.60, 71.99 and 80.06% at doses of 12.5 and 25 mg/kg of trachylobane-360 and 25 mg/kg of 5-FU, respectively. Biochemical parameters were not altered. Leukopenia was observed after 5-FU treatment, but this effect was not seen with trachylobane-360 treatment. The histopathological analysis of liver and kidney showed that both organs were mildly affected by trachylobane-360 treatment. Trachylobane-360 showed no immunosuppressive effect. In conclusion, these data reinforce the anticancer potential of this natural diterpene.

WGA, an agglutinin from wheat germ which is largely responsible for many of wheat’s allergies, was used as a model to investigate the action of ionising radiation on WGA’s anti-nutritive effects in sensitised mice. Based on the molecular structure, the present study also examined the structural modification of WGA in relation to the range of dose. Structural integrity was monitored using HPLC, fluorescence spectrometry and circular dichroism. Results showed a loss of intrinsic activity and the formation of insoluble amorphous aggregates with a lack of native conformational structures after irradiation. Current findings suggest that the allergenic epitopes of WGA became less active and antigenic after high-dose radiation. The reduction of cytokines typical of allergic reactions, with decreased lymphocytic infiltrate, was observed in the gut of mice given irradiated versus native WGA. Food irradiation proved effective and safe in combating immunological and allergic effects of WGA.

Gamma radiation alters the molecular structure of biomolecules and is able to mitigate the action of snake venoms and their isolated toxins. The effect of γ-radiation on the folding of Bothrops lecurus venom lectin was measured by a hemagglutinating assay, intrinsic and bis-ANS fluorescence. Intrinsic and bis-ANS fluorescence analyses indicated that irradiation caused unfolding followed by aggregation of the lectin. Our results suggest that irradiation can lead to significant changes in the protein structure, which may promote the loss of its binding property and toxic action.

In the study, we have examined the antitumor and antimicrobial activities of the methanol extract, the fractions, a fraction of total alkaloids and two alkaloids isolated from the stem of Erythroxylum caatingae Plowman. All test fractions, except the hexane fractions, showed antimicrobial activity on gram-positive bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice was observed in these fractions and 6β-Benzoyloxy-3α-(3,4,5- trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC-1 was used to verify the mechanism of action of the compounds of E. caatingae that showed cytotoxicity less than 30 μg/mL in leukemic cells. After 48 h of incubation, we observed that the acetate: methanol (95:5), acetate, and chloroform fractions, as well as the catuabine B, increased in the number of cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the mitochondrial membrane by incorporation of JC-1 showed that most cells during incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and 59.2%) were stained, suggesting the involvement of an intrinsic pathway of apoptosis.

Leishmania (L.) chagasiis the etiological agent of visceral leishmaniasis, an important endemic zoonosis in the American continent, as well as in many other countries in Asia, Africa, and Mediterranean Europe. The treatment is difficult due to the high toxicity of the available drugs, high costs, and emergence of resistance in the parasites. Therefore, there is an urgent need for new leishmanicidal agents. The bisbenzylisoquinoline alkaloids have been related to antibacterial, antiprotozoal, and antifungal activities. The aim of this study was to evaluate the growth inhibitory activity of warifteine (bisbenzylisoquinoline alkaloid) againstL. chagasipromastigotes in axenic cultures and the occurrence of drug-induced ultrastructural changes in the parasite. This bisbenzylisoquinoline alkaloid was isolated from the leaves and roots ofCissampelos sympodialisEichl. (Menispermaceae), a plant commonly used for the treatment of various diseases in Brazilian folk medicine. Using the purified warifteine, the 50% inhibitory concentration (IC50) was determined at 0.08 mg/mL after 72 h in culture, inducing significant changes in the parasite morphology, like aberrant multisepted forms and blebs in the plasma membrane. In conclusion, warifteine represents an attractive candidate for future pharmacological studies aiming new leishmanicidal drugs.

Crataeva tapia bark lectin was evaluated for its antitumor activity against sarcoma 180 in Swiss albino mice. The anti-inflammatory and analgesic properties were investigated in models of inflammation and nociception. The anti-inflammatory assay was induced by carrageenan induced peritonitis and the analgesic activity was induced by acetic acid-induced writhing response. The lectin presents low toxicity with a LD50 of 2,500 mg/kg body weight and significant antitumor activity causing inhibition of tumor growth. The lectin also promoted significant reduction (35.4%) in the number of neutrophil migration induced by carrageenan. Concerning its analgesic property, the lectin inhibits abdominal contractions induced by acetic acid. The current results revealed a lectin with significant antitumoral, anti-inflammatory and antinociceptive activities. Further investigations to unveil the exact mechanisms are needed.

New 2-isoxazoline aldehydes were synthesized, in good yields, from cycloadduct of the 1,3-dipolar cycloaddition reaction between endocyclic enecarbamate and carboethoxyformonitrile oxide (CEFNO). Condensation of these 2-isoxazoline aldehydes with several phenyl-hydrazines produced new isoxazolyl-aryl-hydrazones, which showed low toxicity and excellent antinociceptive activity, when compared to dipyrone. The antinociceptive activity of isoxazolyl-aryl-hydrazones was performed using the acetic acid-induced mice abdominal constrictions test.

Spondias mombin L. (yellow mombin) is a tree with a nutritional fruit that is commonly consumed in the North and Northeast of Brazil, as the juice of its pulp is rich in antioxidant compounds. This study aimed to investigate the gastroprotective and ulcer healing activities of yellow mombin juice (YMJ) in Wistar rats, and to elucidate the possible involved mechanisms. Phytochemical characterization of the lyophilized fruit juice was performed by high-performance liquid chromatography (HPLC). The gastroprotective activity of YMJ was investigated in ethanol (25, 50, and 100% YMJ) and indomethacin (100% YMJ) models of acute gastric ulcer in rats. Then, the effect of YMJ on mucus production and gastric secretions, and the involvement of non-protein sulfhydryl groups and prostaglandins in the gastroprotective process were examined. Moreover, the ulcer healing effect of YMJ was investigated in a model of acetic acid-induced chronic ulcer through histological and immunohistochemical analyses. HPLC results identified the presence of epicatechin (7.1 ± 1.6 μg/mL) and quercetin (17.3 ± 2.5 μg/mL) in YMJ. Ethanol-induced gastric lesions were inhibited by YMJ (25, 50, and 100%) by 42.42, 45.09, and 98.21% respectively, and indomethacin-induced lesions were inhibited by YMJ (100%) by 58.96%, compared to control group. Moreover, YMJ reduced gastric content and total acidy by 57.35 and 71.97%, respectively, compared to the control group. Treatment with YMJ also promoted healing of chronic ulcer, regeneration of the gastric mucosa, and restoration of mucus levels in glandular cells, as confirmed by histological analysis. It also increased cellular proliferation, as demonstrated by high reactivity to Ki-67 and bromodeoxyuridine. In conclusion, YMJ was found to possess gastroprotective and ulcer healing activities that are correlated to its antisecretory action. These results support the commercial exploration of YMJ as a functional food.

Objectives Novel 5-benzilidene thiazolidinones have been synthesized and exhibited anti-inflammatory activity. In this work one of the compounds of the thiazolidinone chemical series, (5Z,E)-3-[2-(4-chlorophenyl)-2-oxoethyl]-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (PG15) was investigated aiming to determine the drug's anti-inflammatory potential in pre-clinical studies. Methods Methods used included the in-vitro inhibition of cyclooxygenase-1 and -2, in-vivo evaluation of anti-inflammatory activity by air pouch and peritonitis models and the pharmacokinetic profile after intravenous (3 mg/kg) and oral (3 and 6 mg/kg) dosing to rats. Key findings A two-compartment model with a fast distribution and an elimination half-life of 5.9 +/- 3.8 h described the PG15 plasma profile after intravenous dosing. PG15 showed an erratic and rapid absorption following oral administration with peak concentrations between 0.5 and 1 h. PG15 0.1 microM inhibited more than 30% and 13% of purified cyclooxygenase-1 and -2 activity in vitro, respectively. A lack of dose dependency was observed for the anti-inflammatory effect in the dose range investigated (0.8-50 mg/kg), with a maximum of 67.2 +/- 4.6% inhibition of leucocyte migration in the carrageenan-induced air pouch model obtained with the 3 mg/kg dose, similar to that observed for indometacin 10 mg/kg. Conclusions The erratic absorption of PG15 observed after oral dosing could explain the lack of anti-inflammatory dose dependency.

Ethnopharmacological relevance In this study, we investigated the role of local perceptions of diseases in the selection of medicinal plants. For this purpose, we consulted local experts from two communities located in the semiarid region of northeastern Brazil. Materials and methods After selecting the experts, we used semi-structured interviews to assess the symptoms of each disease studied, the perception of variations in each of these diseases, and the plants used for their treatment. We then conducted a participatory workshop in which the experts engaged in free grouping of the diseases mentioned in the first step. Results We observed that the therapeutic targets (diseases) showed a lower similarity of medicinal plants than the perceived variants of these targets. We found that plant selection was associated with the perception of symptoms: the greater the similarity between two diseases based on the perceived symptoms, the greater the similarity between these diseases based on the medicinal plants. Furthermore, we observed a greater similarity between plants used to treat diseases perceived as related to each other. Conclusion Local perceptions of the association between diseases and between diseases and symptoms can influence plant selection such that the similarity of the medicinal plants chosen is higher for the diseases perceived as related and as having common symptoms. These results indicate the presence of mechanisms by which local perceptions of diseases affect the structures of local medical systems.

Studies suggest that inflammation is a key factor in the pathogenesis of diabetes mellitus. Pro-inflammatory cytokines, such as IL-6 and TNF-alpha, are produced by adipose tissue in large quantities, in obese and especially in diabetic individuals. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with anti-inflammatory and antioxidant actions that may contribute to alleviate diabetes side effects, as neuropathy, retinopathy and nephropathy. This study aims to investigate PTX anti-inflammatory effects on the carrageenan-induced paw edema model, in alloxan-induced diabetic rats. Diabetic animals (male Wistar rats, 200 – 250 g) were daily treated with PTX (25, 50, 100 mg/kg, p.o.), glibenclamide (GLI, 5 mg/kg, p.o., as reference) or water, for 5 days. Afterwards, carrageenan-treated paws were dissected, their skin removed and the tissue used for preparation of homogenates and measurements of IL-6 and TNF-alpha by Elisa. Serum levels of nitrite were also deter mined and paw slices used for iNOS immunohistochemistry assays. We showed that diabetic rats presented an amplificat ion of the inflammatory response, as related to non-diabetic rats, what was evident 48 h after the edema-induction. The PTX -treatment of diabetic rats re ducedglycemia(asrelatedto untreated-diabetic ones) and the paw edema. It also brough t edema volumes to values sim ilar to those of non-diabetic rats, at the same observation time. The increased TNF-alpha and IL-6 levels in paws of untreated-diabetic rats were reduced in diabetic animals after PTX treatments. Besides, the increased levels of nitrite in the serum of diabetic rats were also decreased by PTX. Furthermore, a higher number of iNOS immunostained cells was demonstrated in paw tissues from untreated-diabetic rats, as related to those of PTX-treated diabetic animals. Our results show that PTX reduces inflammatory parameters, as pro-inflammatory cytokines and iNOS expression, indicating the potential benefit of the drug for the treatment of diabetes and related pathologic conditions.

A new method for the synthesis of [3,1]-benzothiazepines and [3,1]-benzoxazepines from the reaction of C-allylanilines and isothiocyanates or isocyanates without the need for the isolation of any intermediate is described. The compounds were obtained in good to moderate yields and some exhibited cytotoxic activity against tumor cell lines.

Among all derivatives synthesized, compound (IId) is found to be the most active compound against MCF-7, HT-29, NCI-H292, HL-60, and K562 cancer cell lines.

The chemical composition, antitumor activity and toxicity of the essential oil from Lippia microphylla leaves (OEL) were investigated. The major constituents were thymol (46.5%), carvacrol (31.7%), p-cymene (9%), and γ-terpinene (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay with Swiss mice erythrocytes was performed. The concentration producing 50% hemolysis (HC50) was 300 μg/mL. Sarcoma 180 tumor growth was inhibited in vivo 38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86% inhibition. OEL displays moderate gastrointestinal and hematological toxicity along with causing some alteration in liver function and morphology. However, the changes were considered reversible and negligible in comparison to the effects of several anticancer drugs. In summary, OEL displays in vivo antitumor activity and a moderate toxicity, which suggests further pharmacological study.

This study aimed to study the in vitro antioxidant activity and cytotoxicity on tumor cells lines of six synthetic substances derived from riparins. All the substances showed antioxidant activity and riparins C, D, E, F presented cell growth inhibition rates greater than 70%, suggesting that these molecules have antitumor properties. These substances also caused greater than 80% releases of cytoplasmic lactate dehydrogenase enzyme (LDH). Although the antioxidant and antitumor properties presented herein require further assessment, the outcomes indicate that these novel riparins are promising biologically active compounds.

Croton zehntneri (Euphorbiaceae) is a native aromatic plant from Northeast region of Brazil. The monoterpenoid estragole (ESL) has been isolated by classical chromatographic methods from the essential oil (EO) of C. zehnteneri leaves and characterized by GC-FID and GC-MS, its antimicrobial and cytotoxic potentials being assessed. The analysis of the EO enabled the identification of 100% of the integrated constituents, of which yield was about 1.8%. The main components identified were: eucalyptol, estragole (84.7%) and spathulenol. The dosage of 50 μg/disk of ESL presented fairly significant zones of inhibition against Gram-positive bacteria and fungi. The ESL presented toxicity against Artemia salina with LC50 and LC90 of 4,54 and 8,47 μg mL-1. However, in tumor inhibition assays (human cells), there were no rewarding inhibition in any of the human cancer cell lines (MCF-7, HEP-2 and NCI-H292). Croton zehntneri (Euphorbiaceae) é uma planta aromática nativa da região Nordeste do Brasil. O monoterpenóide Estragol (ESL) foi isolado por métodos cromatográficos clássicos a partir do óleo essencial (OE) das folhas de C. zehntneri e caracterizado por CG-DIC e CG-EM, tendo seu potencial antimicrobiano e citotóxico avaliado. A análise do OE permitiu a identificação de 100% dos constituintes integrados, cujo rendimento foi cerca de 1.8%. Os principais componentes identificados foram: eucaliptol, estragol (84.7%) e espatulenol. A dosagem de 50 μg/disco de ESL apresentou halos de inibição bastante expressivos frente a bactérias gram positiva e fungos. O ESL apresentou toxicidade frente a Artemia salina com CL50 e CL90 de 4,54 e 8,47 μg mL-1. Entretanto, nos testes de inibição tumoral (células humanas), não houve inibição satisfatória em nenhuma das linhagens de células humanas cancerígenas (MCF-7, HEP-2 e NCIH292).

A new method for the synthesis of [3,1]-benzothiazepines and [3,1]- benzoxazepines from the reaction of C-allylanilines and isothiocyanates or isocyanates without the need for the isolation of any intermediate is described. The compounds were obtained in good to moderate yields and some exhibited cytotoxic activity against tumor cell lines. Benzothiazepines and benzoxazepines constitute important building blocks in pharmaceutical research while they can be found in many drugs and preclinical leads.1 The synthesis of different isomeric forms of these compounds by varying the position of the heteroatoms in their structures together with their unique pharmacological properties make the development of new methods for the synthesis of medium-sized heterocycles containing N, S and O atoms a subject of great interest. Thus, several isomers of benzothiazepine2 and benzoxazepine3 rings were already described and some of them exhibited a wide variety of pharmacological effects.4

The essential oils fromMangifera indicavar. Rosa and Espada latex were obtained by hydrodistillation and analyzed using GC-FID and GC-MS. Twenty-seven components were identified. The main compound in the essential oil fromM. indicavar. Espada (EOMiE) was terpinolene (73.6%). The essential oil ofM. indicavar. Rosa (EOMiR) was characterized by high amounts ofβ-pinene (40.7%) and terpinolene (28.3%). In the test for leishmanicidal activity against promastigotes forms ofL. amazonensis, EOMiR and EOMiE showed IC50(72 h) of 39.1 and 23.0 μg/mL, respectively. In macrophages, EOMiR and EOMiE showed CC50of 142.84 and 158.65 μg/mL, respectively. However, both were more specific to the parasite than macrophages, with values of selectivity index of 6.91 for EOMiE and 3.66 for EOMiR. The essential oils were evaluated for their cytotoxicity against the human tumor cells HEp-2, HT-29, NCI-H292, and HL-60. The EOMiR and EOMiE were most effective against the HL-60, with IC50values of 12.3 and 3.6 μg/mL, respectively. The results demonstrated that the essential oils ofM. indicacan destroyL. amazonensisand inhibit tumor cell growth. These findings contribute to the knowledge of the Brazilian biodiversity as a source of potential therapeutic agents.

This paper presents an investigation on the cytotoxic activity in human tumor cell from dichloromethane, chloroform, methanol, ethanol, water extracts, and hexane and chloroform fractions from green, brown and red algae collected at Riacho Doce Beach, north coast of Alagoas, Brazil, against the cancer cells K562 (chronic myelocytic leukemia), HEp-2 (laryngeal epidermoid carcinoma) and NCI-H292 (human lung mucoepidermoid carcinoma) through the MTT colorimetric method. The dichloromethane extract and chloroform fraction of Hypnea musciformis showed the best cytotoxic activity against K562 (3.8±0.2 μg.mL-1 and 6.4±0.4 μg.mL-1, respectively). Dichloromethane extracts of Dictyota dichotoma (16.3±0.3 μg.mL-1) and the chloroform fraction of H. musciformis (6.0±0.03 μg.mL-1) and chloroform fraction of P. gymnospora (8.2±0.4) were more active against HEp-2 as well as ethanol extracts of P. gymnospora (15.9±2.8 μg.mL-1) and chloroform fraction of H. musciformis (15.0±1.3 μg.mL-1) against the cell NCI-H292. The constituents with higher anticancer action are present in the extracts of dichloromethane and chloroform and in the chloroform fraction of H. musciformis, Digenea simplex, P. gymnospora, and D.dichotoma. In the case of the seaweed S. vulgare, the anticancer constituents are present in the aqueous extract. Keywords: seaweed, cancerous cells, cytotoxicity, algae extract

(−)-Massoialactone, an α,β-unsaturated δ-lactone isolated from Cryptocarya massoia, and five analogues were synthesized and their antiproliferative and anti-inflammatory activities were evaluated. The lactones were able to mimic the “core” functional group required for the biological activity of their parent natural compounds suggesting that substantially altered analogues may retain their properties.

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 48 hours 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 0.82 g 5-FU per 1.0 g 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 48 hours. 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.

The lichen Cladonia verticillaris produces bioactive secondary metabolites, such as fumarprotocetraric (FUM) and protocetraric acids. Species of the genus Cladonia demonstrate anti-tumor, anti-inflammatory and antipyretic activities and have been used in folk medicine to treat respiratory diseases (throat irritation, cough, asthma and tuberculosis). The aim of the present study was to evaluate the expectorant and mucolytic activities of fumarprotocetraric acid in albino Swiss mice. FUM was extracted and purified from an acetone extract of C. verticillaris. The phenol red quantification method was used on the bronchoalveolar lavage fluid following the administration of FUM (25, 50 or 100 mg/kg orally or intraduodenally and 12.5, 25 or 50 mg/kg, intraperitoneally) for the evaluation of expectorant activity. Control groups received either saline solution (7.5 mL/kg) or ambroxol (1 mg/kg) through the same administration routes. Antioxidant activity was evaluated using the thiobarbituric acid reactive species assay in mouse lung tissue treated with the FUM at 25, 50 or 100 mg/kg orally, followed by a lipopolysaccharide solution at 1 mg/kg intrapleurally. The same protocol was used for the control groups using either saline solution (7.5 mL/kg, orally) or N-acetylcysteine (20 mg/kg, orally). Results: Orally administered FUM at doses of 25 and 50 mg/kg promoted significantly greater dose-dependent phenol red activity in the bronchoalveolar lavage and expectorant activity in comparison to the controls (p < 0.05). Lipid peroxidation (malondialdehyde equivalent) was reduced by 50% in the lung tissue. Conclusion: The results confirm the expectorant and antioxidant properties of fumarprotocetraric acid produced by the lichen C. verticillaris.

The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oilin natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When usedin naturaor in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

Due to its folk use, scientific reports and phytochemical screening, the purpose of this work was to study the phytochemical and the biological properties of the methanol extract and to evaluate the anti-inflammatory activity as well as determine the acute toxicity, antitumor and cytotoxic activity of the root barks of Guettarda platypoda DC., Rubiaceae. In this analysis the presence of flavonoids and therpenoids were identified. These data and the ones in the literature indicated it as a potential antioxidant and motivated the cytotoxic analysis related with three tumoral cell strains as well as to evaluate its antitumoral activity (sarcoma 180 and Ehrlich carcinoma) in female mice. Due to the presence of esteroids and the previous study of the ethanolic extract, its anti-inflammatory activity and toxicity were also evaluated. Absence or low toxicity in 2000 mg/kg doses was verified and the attention to their phytochemical and pharmacological properties is constantly increasing.

Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart. (Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases. The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models. The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.

Microorganisms with immunomodulating effects beneficially affect the host organism by improving the microbial equilibrium and balancing the immune system. Zymomonas mobilis is reported to have antagonistic properties against yeast and other pathogenic microorganisms in humans and animals. This study assessed the effects of Z. mobilis UFPEDA 202 (10(9)CFU/mL) cultures on polymicrobial sepsis induced by cecal ligation and puncture (CLP). The survival of animals subjected to lethal sepsis was evaluated after pre-treatment, post-treatment or a combination of both. 6h after the induction of sepsis, neutrophil migration, the number of bacteria, myeloperoxidase, TNF-α, MCP-1, and IL-10 were performed in the peritoneal lavage of animals. Histopathological changes in the spleen of animals were evaluated by light microscopy, and apoptosis of splenocytes was analyzed by transmission electron microscopy. The results showed that the combination of prophylactic and therapeutic treatment with Z. mobilis increased the survival of animals by 50% at 96 h after the induction of sepsis. There was a reduction in the levels of TNF-α and myeloperoxidase (MPO) in lung tissue. There was also a reduction in the number of viable bacteria in peritoneal fluid. However, increases in neutrophil migration and IL-10 levels were observed. The observed levels of MCP-1 remained similar to the control. Histopathology analysis showed a decrease in acute lung injury. The group pre-treated with the Z. mobilis culture demonstrated a marked decrease in the number of apoptotic cells in the spleen (24%). This study demonstrates that Z. mobilis cultures increased the survival of animals with severe sepsis. This survival was mediated by improvement of neutrophil migration, enhanced activity against pathogenic enteric bacteria and reduced lung injury.

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.

Neoplastic transformation is the abnormal proliferation of cells. These transformations are often related to changes in cell surface glycoconjugates which can be detected by lectins. We evaluated the anti-tumor potential of BlL, a galactoside-binding lectin isolated from Bothrops leucurus venom as well as its cytotoxicity and hemolysis activity. The phosphatidylserine externalization and mitochondrial membrane potential were also determined. BlL exhibited cytotoxic activity against all tumor cell lines tested by induced phosphatidylserine externalization and mitochondrial depolarization, indicating cell death by apoptosis.

Aim The intent of this study is to examine whether intrauterine malnutrition provokes alterations in the progression of the acute and subchronic inflammatory response, and its influence on the pharmacological effect of indomethacin. Methods design Rat offspring of dams which were fed from the first day of their gestation to term receiving a balanced diet (Labina) or a basic regional diet (BRD) from northeastern Brazil. According to their dams, the offspring were divided in two groups: Control-N (nourished) and BRD-g (undernourished during gestation). At 2 months of age, the animals were divided into groups (n = 06): (1) Animals that were subjected to carrageenan or (2) zymosan-induce paw edema (acute inflammation models) and (3) Animals that were subjected to cotton pellet-induced granuloma (subchronic inflammation model). All animals received (saline 0.9%; p.o.). Another set of adult offspring was submitted to the same procedure as above, but instead of saline they received (via gavage) a single oral dose of indomethacin (10 mg/kg) for the animals subjected to acute inflammation models or 2 mg/kg for seven consecutive days for the animals subjected to subchronic inflammation model. The animals were further divided in two groups: Control-NI (Control-N treated with indomethacin), and BRDI-g (BRD-g treated with indomethacin). The volume of hind paw swelling (mL) was measured at time zero (before), 30, 60, 120, 180 and 240 min after carrageenan or zymosan injection. In the subchronic model of inflammation, the pellets were removed and dried to a constant weight. Hind paw swelling, weight of granuloma, blood albumin and C-reactive protein (CRP) levels, leukocyte count and cytokine levels were evaluated as indicators of inflammation. Results Undernutrition during pregnancy caused fetal growth retardation which was shown in terms of low birth weight (5.38 ± 0.28), when compared to the Control-N (7.26 ± 0.64) group. The volume of paw edema, the serum levels of CRP and albumin and cytokine levels were lower than those in the BRD-g group when compared to those in the Control-N groups, in both models of acute inflammation studied. However, no difference was found in the total leukocyte count. When compared to the respective groups treated with saline (Control-N and BRD-g), the antiinflammatory effect of indomethacin in the animals of BRDI-g groups was lower than in the Control-NI groups, in the model of acute inflammation. In the model of subchronic inflammation, the pharmacological effect of indomethacin was effective only in nourished animals. Conclusion Malnutrition in the early stages of development attenuated the severity of the acute inflammatory response, but there was no statistically significant change in subchronic inflammation induced by granulomatous lesion. Our findings provide impetus for larger trials to assess the influence of undernutrition on the pharmacokinetics/pharmacodynamics of indomethacin.

The objective of the present study was to investigate whether early undernutrition changes the chronic inflammatory response, so as to study its influence on pharmacological response to indomethacin. Rat offspring of dams fed from the first day of gestation to term or throughout the lactation period received a balanced diet (NN) or a basic regional diet (BRD) from northeast Brazil. According to their dams, the offspring were divided into three groups: NN; basic regional diet during gestation (BRD-g, undernourished during gestation); basic regional diet during gestation and lactation (BRD-gl, undernourished during gestation and lactation). At 2 months of age, Freund's adjuvant (0·2 ml) was inoculated into the plantar surface of the hind paw (day 0) of animals. All animals orally received saline (0·9 %) for 28 d. Another group of adult offspring was subjected to the same procedure as described above, but orally received indomethacin (2 mg/kg) instead of saline, and divided into three subgroups: NN treated with indomethacin (NNI); BRD-g treated with indomethacin (BRDI-g); BRD-gl treated with indomethacin (BRDI-gl). The hind paw volume was calculated on days 0 (initial paw volume), 7, 14 and 28. Hind paw swelling, blood albumin and C-reactive protein (CRP) levels and leucocyte counts were evaluated as markers of inflammation. Reduced hind paw swelling and the blood levels of serum albumin and CRP were found in the BRD-g and BRD-gl offspring. However, no difference was found in the leucocyte count. Compared with their respective saline-treated groups (NN, BRD-g and BRD-gl), the anti-inflammatory effect of indomethacin was lower in the BRDI-g and BRDI-gl groups than in the NNI group. We conclude that early undernutrition attenuated the chronic inflammatory response and the anti-inflammatory effect of indomethacin.

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. Docking studies with these compounds indicated that they exhibit specific interactions with key residues located in the site of the PPARgamma structure, which corroborates the hypothesis that these molecules are potential ligands of PPARgamma. In addition, competition binding assays showed that four of these compounds bound directly to the ligand-binding domain of PPARgamma, with reduced affinity when compared to rosiglitazone. An important trend was observed between the docking scores and the anti-inflammatory activities of this set of molecules. The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, explained why the 3-(2-bromo-benzyl)-5-(4-methanesulfonyl-benzylidene)-thiazolidine-2,4-dione compound had the best activity and the best docking score. Almost all of the stronger hydrophilic interactions occurred between the substituted 5-arylidene group of this compound and the residues of the binding site.

A novel set of acridinylidene thiazolidinediones and benzylidene thiazolidinediones was synthesized by nucleophilic addition of cyanoacrylates. Some of these compounds were evaluated for their glucose lowering capability and their effects on the triglyceride level in alloxan diabetic mice.

Background Streptomyces hygroscopicusis a species that produces a variety of antibiotics belonging to different classes. It has a distinct structure and possesses certain biological properties, such as antimicrobial and antitumor [1]. According to a study by Rong and Huang (2012) [2] more than 650 kinds of bioactive substances have been produced by Streptomyces hygroscopicus and species related to it. Members of this clade are still one of the main means of screening new substances. The aim of this study was to investigate the antioxidant activity and chemical profile of metabolites of Streptomyces hygroscopicus S75-5 obtained by fermentation in liquid and solid media. The antioxidant activity evaluation was conducted using the DPPH method [3] and chemical prospecting following the methodology described by Harborne [4]. The results showed that the extracts of fermentation in the liquid medium presented the highest percentage of antioxidant activity. Chemical prospecting also made it possible to determine the presence of phenolic compounds in the ethyl acetate extract of the metabolic liquid by fermentation in a liquid medium.