The healing effect of a mixture of Arnebia euchroma and animal fat on burn wounds in rats in comparison with sulfadiazine.

OBJECTIVE: Thermal burn is a serious cause of morbidity and mortality that affects millions of people worldwide. The aim of this experimental study was to investigate the efficacy of Arnebia euchroma (AE) to treat burn wounds in a rat model. METHOD: A total of 80 male rats (200-250g) were shaved over the back of the neck (2×3cm2) and a second-degree burn wound was induced at this site under general anaesthesia. The rats were then randomly assigned to one of four groups (each n=20) and the burns were treated daily for 14 days as follows: (1) dressed with animal fat; (2) dressed with sulfadiazine; (3) dressed with a mixture of AE and animal fat; (4) no treatment (control). Five rats from each group were sacrificed on days 3, 5, 9 and 14 post-burn and the wounds were evaluated histologically and immunohistochemically for the expression of interleukin (IL)-1 and IL-6. RESULTS: There was a significant increase at day 3 and decrease on day 5 samples for the expression of IL-1 in the AE plus fat group and IL-6 in the AE plus fat and sulfadiazine groups, compared to the control and fat treatment groups, respectively. Both AE plus fat and sulfadiazine treatments reduced inflammation and granulation tissue formation by day 5 post-burn, while re-epithelialisation commenced by day 9 post-burn. In addition, burns treated with AE plus fat exhibited keratinised epidermis, associated with regular collagen fibres, compared to moderately dense collagen fibres without vascularisation in the sulfadiazine group. CONCLUSION: These findings suggested that AE plus fat was superior to sulfadiazine in enhancing burn wound healing in rats.

Evaluation of the effect of guanabenz-loaded nanoparticles on chronic toxoplasmosis in mice.

Chronic toxoplasmosis which is positively correlated with many neuropsychiatric problems has no curative treatment till now; due to the resistant tissue cysts especially in the brain. In search of an effective treatment, guanabenz-loaded polyethylene glycol poly lactic-co-glycolic acid (PEG-PLGA) nanoparticles was evaluated against chronic experimental toxoplasmosis. For this purpose, each mouse was infected with 10 cysts of Toxoplasma gondii (ME 49 strain). Treated mice received either guanabenz alone (5 mg/kg/day) in subgroup IIa or guanabenz-loaded nanoparticles by full dose in subgroup IIb or guanabenz-loaded nanoparticles by the half dose (2.5 mg/kg/day) in subgroup IIc. Subgroup Ie was treated by pyrimethamine and sulfadiazine. The treatment started on day 25 post-infection for 19 successive days. Then Parasitological, histopathological, immunohistochemical, immunological and ultrastructural morphological studies were performed. The results showed that: subgroup IIb showed the highest statistically significant reduction in the neuroinflammation and brain tissue cysts (77%) with a significant higher efficacy in comparison with pyrimethamine and sulfadiazine and showed the highest level of IFN-γ, while the lowest level was in subgroup IIa. All group II mice showed similar changes of depression and compression of the wall of the cyst. This is marked in subgroup IIb with release of crescent shaped bradyzoite outside the cyst. PEG-PLGA nanoparticles had no toxic effect on the liver or the kidney of the mice. It could be concluded that guanabenz-loaded PEG-PLGA nanoparticles could be promising and safe for treatment of chronic toxoplasmosis.

Sulfadiazine analogs: anti-Toxoplasma in vitro study of sulfonamide triazoles.

Toxoplasmosis is an infection that prevails all over the world and is caused by the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii). Promising novel compounds for the treatment of T. gondii are introduced in the current investigation. In order to test their in vitro potency against T. gondii tachyzoites, six 1,2,3-triazoles-based sulfonamide scaffolds with terminal NH2 or OH group were prepared and investigated as sulfadiazine equivalents. When compared to sulfadiazine, which served as a positive control, hybrid molecules showed much more anti-Toxoplasma activity. The results showed that the IC50 of the examined compounds 3(a-f) were recoded as 0.07492 µM, 0.07455 µM, 0.0392 µM, 0.03124 µM, 0.0533 µM, and 0.01835 µM, respectively, while the sulfadiazine exhibited 0.1852 µM. The studied 1,2,3-triazole-sulfadrug molecular conjugates 3(a-f) revealed selectivity index of 10.4, 8.9, 25.4, 21, 8.3, and 29; respectively. The current study focused on the newly synthesized amino derivatives 3(d-f), as they contain the more potent amino groups which are recognized to be essential elements and promote better biological activity. Extracellular tachyzoites underwent striking morphological alterations after 2 h of treatment as seen by scanning electron microscopy (SEM). Additionally, the intracellular tachyzoite exposed to the newly synthesized amino derivatives 3(d-f) for a 24-h period of treatment revealed damaged and altered morphology by transmission electron microscopic (TEM) indicating cytopathic effects. Moreover, compound 3f underwent the most pronounced changes, indicating that it had the strongest activity against T. gondii.

Inhibition of Toxoplasma gondii by 1,2,4-triazole-based compounds: marked improvement in selectivity relative to the standard therapy pyrimethamine and sulfadiazine.

A safer treatment for toxoplasmosis would be achieved by improving the selectivity profile of novel chemotherapeutics compared to the standard therapy pyrimethamine (PYR) and sulfadiazine (SDZ). We previously reported on the identification of the compounds with imidazole-thiosemicarbazide scaffold as potent and selective anti-Toxoplasma gondii (T. gondii) agents. In our current research, we report on the optimisation of this chemical scaffold leading to the discovery cyclic analogue 20 b with s-triazole core structure. This compound displayed prominent CC30 to IC50 selectivity index (SI) of 70.72, making it 160-fold more selective than SDZ, 11-fold more selective than PYR, and 4-fold more selective than trimethoprim (TRI). Additionally, this compound possesses prerequisite drug-like anti-Toxoplasma properties to advance into preclinical development; it showed ability to cross the BBB, did not induce genotoxic and haemolytic changes in human cells, and as well as it was characterised by low cellular toxicity.

Dextran Fluorescent Probes Containing Sulfadiazine and Rhodamine B Groups.

Fluorescent imaging has been expanded, as a non-invasive diagnostic modality for cancers, in recent years. Fluorescent probes in the near-infrared window can provide high sensitivity, resolution, and signal-to-noise ratio, without the use of ionizing radiation. Some fluorescent compounds with low molecular weight, such as rhodamine B (RhB) and indocyanine green (ICG), have been used in fluorescent imaging to improve imaging contrast and sensitivity; however, since these probes are excreted from the body quickly, they possess significant restrictions for imaging. To find a potential solution to this, this work investigated the synthesis and properties of novel macromolecular fluorescent compounds. Herein, water-soluble dextran fluorescent compounds (SD-Dextran-RhB) were prepared by the attachment of RhB and sulfadiazine (SD) derivatives to dextran carrier. These fluorescent compounds were then characterized through IR, 1H NMR, 13C NMR, UV, GPC, and other methods. Assays of their cellular uptake and cell cytotoxicity and fluorescent imaging were also performed. Through this study, it was found that SD-Dextran-RhB is sensitive to acidic conditions and possesses low cell cytotoxicities compared to normal 293 cells and HepG2 and HeLa tumor cells. Moreover, SD-Dextran-RhB demonstrated good fluorescent imaging in HepG2 and HeLa cells. Therefore, SD-Dextran-RhB is suitable to be potentially applied as a probe in the fluorescent imaging of tumors.

Sulfadiazine Masquerading as a Natural Product from Scilla madeirensis (Scilloideae).

The structure of 2,4-(4'-aminobenzenamine)pyrimidine (1), a pyrimidine alkaloid previously isolated from the bulbs of Scilla madeirensis (Asparagaceae, synonym Autonoë madeirensis), has been revised. These conclusions were met via comparison of reported NMR and EIMS data with those obtained from synthetic standards. The corrected structure is the antibiotic sulfadiazine (2), which has likely been isolated as a contaminant from the site of collection. The reported bioactivity of 1 as an α1-adrenoceptor antagonist should instead be ascribed to sulfadiazine. Our findings appear to show another example of an anthropogenic contaminant being identified as a natural product and emphasize the importance of considering the biosynthetic origins of isolated compounds within a phylogenetic context.

Synthesis of sulpha drug based hydroxytriazene derivatives: Anti-diabetic, antioxidant, anti-inflammatory activity and their molecular docking studies.

Herein, we report synthesis, characterization, anti-diabetic, anti-inflammatory and anti-oxidant activities of hydroxytriazenes derived from sulpha drugs, namely sulphanilamide, sulphadiazine, sulphapyridine and sulphamethazine. Before biological screening of the compounds, theoretical prediction using PASS was done which indicates probable activities ranging from Pa (probable activity) values 65-98% for anti-inflammatory activity. As per the predication, experimental validation of some of the predicted activities particularly anti-diabetic, anti-inflammatory and anti-oxidant was done. Anti-diabetic activities have been screened using two methods namely α-amylase and α-glucosidase inhibition method and IC50 values were ranging from 66 to 260 and 148 to 401 µg/mL, while for standard drug acarbose the values were 12 µg/mL and 70 µg/mL, respectively. Docking studies have also been done for antidiabetic target pancreatic alpha amylase. The molecular docking studies in α-amylase enzyme reveal that the middle phenyl ring of all the compounds mainly occupies in the small hydrophobic pocket formed by the Ala198, Trp58, Leu162, Leu165 and Ile235 residues and sulphonamide moiety establish H-bond interaction by two water molecules. Further, anti-inflammatory activity has been evaluated using carrageenan induced paw-edema method and results indicate excellent anti-inflammatory activity by hydroxytriazenes (71 to 97%) and standard drug diclofenac 94% after 4 h of treatment. Moreover, antioxidant effect of the compounds was tested using DPPH and ABTS methods. All the compounds displayed good results (24-488 µg/mL) against ABTS radical and many compounds are more active than ascorbic acid (69 µg/mL) while all other compounds showed moderate activity against DPPH radical (292-774 µg/mL) and ascorbic acid (29 µg/mL). Thus, the studies reveal potential of sulfa drug based hydroxytriazenes as candidates for antidiabetic, anti-inflammatory and antioxidant activities which have been experimentally validated.

Sulfadiazine Sodium Ameliorates the Metabolomic Perturbation in Mice Infected with Toxoplasma gondii.

In this study, we analyzed the global metabolomic changes associated with Toxoplasma gondii infection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected with T. gondii GT1 strain and treated orally with SDZ (250 µg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection. We used ultraperformance liquid chromatography-mass spectrometry to profile the serum metabolomes in control (untreated and uninfected) mice, acutely infected mice, and SDZ-treated and infected mice. Infection induced significant perturbations in the metabolism of α-linolenic acid, purine, pyrimidine, arginine, tryptophan, valine, glycerophospholipids, and fatty acyls. However, treatment with SDZ seemed to alleviate the serum metabolic alterations caused by infection. The restoration of the serum metabolite levels in the treated mice was associated with better clinical outcomes. These data indicate that untargeted metabolomics can reveal biochemical pathways associated with restoration of the metabolic status of T. gondii-infected mice following SDZ treatment and could be used to monitor responses to SDZ treatment. This study provides a new systems approach to elucidate the metabolic and therapeutic effects of SDZ in the context of murine toxoplasmosis.

Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice.

Toxoplasma gondii (T. gondii) is a neurotropic parasite that is associated with various neuropsychiatric disorders. Rodents infected with T. gondii display a plethora of behavioural alterations, and Toxoplasma infection in humans has been strongly associated with disorders such as schizophrenia, in which impaired social behaviour is an important feature. Elucidating changes at the cellular level relevant to neuropsychiatric conditions can lead to effective therapies. Here, we compare changes in behaviour during an acute and chronic T. gondii infection in female mice. Further, we notice that during chronic phase of infection, mice display impaired sociability when exposed to a novel conspecific. Also, we show that T. gondii infected mice display impaired short-term social recognition memory. However, object recognition memory remains intact. Using c-Fos as a marker of neuronal activity, we show that infection leads to an impairment in neuronal activation in the medial prefrontal cortex, hippocampus as well as the amygdala when mice are exposed to a social environment and a change in functional connectivity between these regions. We found changes in synaptic proteins that play a role in the process of neuronal activation such as synaptophysin, PSD-95 and changes in downstream substrates of cell activity such as cyclic AMP, phospho-CREB and BDNF. Our results point towards an imbalance in neuronal activity that can lead to a wider range of neuropsychiatric problems upon T. gondii infection.

Non-Propellant Foams of Green Nano-Silver and Sulfadiazine: Development and In Vivo Evaluation for Burn Wounds.

PURPOSE: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. METHODS: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. RESULTS: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. CONCLUSION: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.

Efficacy of sulfadiazine and pyrimetamine for treatment of experimental toxoplasmosis with strains obtained from human cases of congenital disease in Brazil.

Toxoplasmosis in South America presents great health impacts and is a topic of research interest not only because of the severity of native cases but also due to the predominant atypical genotypes of the parasite circulating in this continent. Typically, symptomatic toxoplasmosis is treated with a combination of sulfadiazine (SDZ) and pyrimethamine (PYR). However, some clinical cases present treatment failures due to an inability of the drugs to control the infection or their significant adverse effects, which can lead to treatment interruption. Although resistance/susceptibility to the aforementioned drugs has been well described for clonal strains of Toxoplasma gondii spread to the Northern Hemisphere, less is known about the South American atypical strains. In this study, the effectiveness of SDZ and PYR for the treatment of mice during acute infection with different atypical T. gondii strains was evaluated. Swiss mice were infected with seven T. gondii strains obtained from newborn patients with congenital toxoplasmosis in Brazil. The infected mice were treated with 10-640 mg/kg per day of SDZ, 3-200 mg/kg per day of PYR, or a combination of both drugs with a lower dosage. The mice were evaluated for parameters including mortality, anti-T. gondii IgG production by ELISA and the presence of brain cysts. In addition, the presence of polymorphisms in the dhps gene was verified by gene sequencing. A descriptive analysis was used to assess the association between susceptibility to SDZ and/or PYR and the genotype. The TgCTBr4 and TgCTBr17 strains (genotype 108) presented lower susceptibility to SDZ or PYR treatment. The TgCTBr1 and TgCTBr25 strains (genotype 206) presented similar susceptibility to PYR but not SDZ treatment. The TgCTBr9 strain (genotype 11) was the only strain with high susceptibility to treatment with both drugs. The TgCTBr13 strain (genotype 208) was not susceptible to treatment with the lower PYR or SDZ doses. The TgCTBR23 strain (genotype 41) was more susceptible to PYR than to SDZ treatment. However, the association of low SDZ and PYR doses showed good efficacy for the treatment of experimental toxoplasmosis with T. gondii atypical strains obtained from newborns in Brazil. A new mutation in the T. gondii dhps gene (I347M) was identified that might be associated with the SDZ low sensitivity profile observed for the TgCTBr4 and TgCTBr17 isolates.

Discovery of Potent and Selective Halogen-Substituted Imidazole-Thiosemicarbazides for Inhibition of Toxoplasma gondii Growth In Vitro via Structure-Based Design.

Employing a simple synthetic protocol, a series of highly effective halogen-substituted imidazole-thiosemicarbazides with anti-Toxoplasma gondii effects against the RH tachyzoites, much better than sulfadiazine, were obtained (IC50s 10.30-113.45 µg/mL vs. ~2721.45 µg/mL). The most potent of them, 12, 13, and 15, blocked the in vitro proliferation of T. gondii more potently than trimethoprim (IC50 12.13 µg/mL), as well. The results of lipophilicity studies collectively suggest that logP would be a rate-limiting factor for the anti-Toxoplasma activity of this class of compounds.

Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition.

BACKGROUND: Chronic infection with the neurotropic parasite Toxoplasma gondii has been implicated in the risk for several neuropsychiatric disorders. The mechanisms, by which the parasite may alter neural function and behavior of the host, are not yet understood completely. METHODS: Here, a novel proteomic approach using mass spectrometry was employed to investigate the alterations in synaptic protein composition in a murine model of chronic toxoplasmosis. In a candidate-based strategy, immunoblot analysis and immunohistochemistry were applied to investigate the expression levels of key synaptic proteins in glutamatergic signaling. RESULTS: A comparison of the synaptosomal protein composition revealed distinct changes upon infection, with multiple proteins such as EAAT2, Shank3, AMPA receptor, and NMDA receptor subunits being downregulated, whereas inflammation-related proteins showed an upregulation. Treatment with the antiparasitic agent sulfadiazine strongly reduced tachyzoite levels and diminished neuroinflammatory mediators. However, in both conditions, a significant number of latent cysts persisted in the brain. Conversely, infection-related alterations of key synaptic protein levels could be partly reversed by the treatment. CONCLUSION: These results provide evidence for profound changes especially in synaptic protein composition in T. gondii-infected mice with a downregulation of pivotal components of glutamatergic neurotransmission. Our results suggest that the detected synaptic alterations are a consequence of the distinct neuroinflammatory milieu caused by the neurotropic parasite.

A new iron(III) complex-containing sulfadiazine inhibits the proliferation and induces cystogenesis of Toxoplasma gondii.

We have previously shown that metallocomplexes can control the growth of Toxoplasma gondii, the agent that causes toxoplasmosis. In order to develop new metallodrugs to treat this disease, we investigated the influence of the coordination of sulfadiazine (SDZ), a drug used to treat toxoplasmosis, on the biological activity of the iron(III) complex [Fe(HBPClNOL)Cl2]·H2O, 1, (H2BPClNOL=N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)(3-chloro)(2-hydroxy)-propylamine). The new complex [(Cl)(SDZ)Fe(III)(µ-BPClNOL)2Fe(III)(SDZ)(Cl)]·2H2O, 2, which was obtained by the reaction between complex 1 and SDZ, was characterized using a range of physico-chemical techniques. The cytotoxic effect of the complexes and the ability of T. gondii to infect LLC-MK2 cells were assessed. It was found that both complexes reduced the growth of T. gondii while also causing low cytotoxicity in the host cells. After 48 h of treatment, complex 2 reduced the parasite's ability to proliferate by about 50% with an IC50 of 1.66 µmol/L. Meanwhile, complex 1 or SDZ alone caused a 40% reduction in proliferation, and SDZ displayed an IC50 of 5.3 µmol/L. In addition, complex 2 treatment induced distinct morphological and ultrastructural changes in the parasites and triggered the formation of cyst-like forms. These results show that the coordination of SDZ to the iron(III) complex is a good strategy for increasing the anti-toxoplasma activity of these compounds.

Evaluation of Veterinary-Specific Interpretive Criteria for Susceptibility Testing of Streptococcus equi Subspecies with Trimethoprim-Sulfamethoxazole and Trimethoprim-Sulfadiazine.

Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim-sulfamethoxazole and/or trimethoprim-sulfadiazine with S. equi This study indicates trimethoprim-sulfamethoxazole as an acceptable surrogate for trimethoprim-sulfadiazine with S. equi.

Association between water and carbon dioxide transport in leaf plasma membranes: assessing the role of aquaporins.

The role of some aquaporins as CO2 permeable channels has been controversial. Low CO2 permeability of plant membranes has been criticized because of unstirred layers and other limitations. Here we measured both water and CO2 permeability (Pos , PCO2 ) using stopped flow on plasma membrane vesicles (pmv) isolated from Pisum sativum (pea) and Arabidopsis thaliana leaves. We excluded the chemical limitation of carbonic anhydrase (CA) in the vesicle acidification technique for PCO2 using different temperatures and CA concentrations. Unstirred layers were excluded based on small vesicle size and the positive correlation between vesicle diameter and PCO2 . We observed high aquaporin activity (Pos 0.06 to 0.22 cm s-1 ) for pea pmv based on all the criteria for their function using inhibitors and temperature dependence. Inhibitors of Pos did not alter PCO2 . PCO2 ranged from 0.001 to 0.012 cm s-1 (mean 0.0079 + 0.0007 cm s-1 ) with activation energy of 30.2 kJ mol-1 . Intrinsic variation between pmv batches from normally grown or stressed plants revealed a weak (R2 = 0.27) positive linear correlation between Pos and PCO2 . Despite the low PCO2 , aquaporins may facilitate CO2 transport across plasma membranes, but probably via a different pathway than for water.

Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells.

Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2. Two antibiotic protocols were evaluated, as follow: i) pre-treatment of T. gondii-tachyzoites with selected antibiotics prior trophoblast infection and ii) post-treatment of infected trophoblasts. The infection index/replication and the impact of the antibiotic therapy on the cytokine milieu were characterized. It was observed that TgChBrUD2 infection induced lower infection index/replication as compared to TgChBrUD1. Regardless the therapeutic protocol, azithromycin was more effective to control the trophoblast infection with both genotypes when compared to conventional antibiotics. Azithromycin induced higher IL-12 production in TgChBrUD1-infected cells that may synergize the anti-parasitic effect. In contrast, the effectiveness of azithromycin to control the TgChBrUD2-infection was not associated with the IL-12 production. BeWo-trophoblasts display distinct susceptibility to T. gondii genotypes and the azithromycin treatment showed to be more effective than conventional antibiotics to control the T. gondii infection/replication regardless the parasite genotype.

Activity of rosuvastatin in tachyzoites of Toxoplasma gondii (RH strain) in HeLa cells.

Due to the toxicity of conventional medication in toxoplasmosis, some drugs are being studied for treating this infection, such as statins, especially rosuvastatin compound, which is efficient in inhibiting the initial isoprenoid biosynthesis processes in humans and the parasite. The goal of this study was to assess the activity of rosuvastatin in HeLa cells infected with the RH strain of T. gondii. In the experiment, HeLa cells (1 × 105) were infected with tachyzoites of T. gondii (5 × 105). After the experimental infection, we assessed the number of infected cells and the amount of intracellular tachyzoites. In addition, culture supernatants were collected to determine the amount of cytokines by cytometric bead array. We observed that there was no cytotoxicity in the concentrations tested in this cell line. The effect of rosuvastatin showed a significant reduction in both the number of infected cells and the proliferation index of the intracellular parasite, when compared with the conventional treatment combining sulfadiazine and pyrimethamine for toxoplasmosis. There were also reduced levels of cytokines IL-6 and IL-17. Therefore, it was concluded that rosuvastatin exhibited antiproliferative activity. The data presented are significant to promote further studies and the search for alternative treatment for toxoplasmosis.

Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity.

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S. aureus, showed the highest susceptibility, with minimum inhibitory concentration values from 7.81 µM. The growth of Candida sp. and Trichophyton interdigitale was inhibited at concentrations starting from 1.95 µM. 4-[(2,5-Dihydroxybenzylidene)amino]-N-(pyrimidin-2-yl)-benzenesulfonamide was identified as the most selective Schiff base for these strains with no apparent cytotoxicity and a selectivity index higher than 16. With respect to M. tuberculosis and M. kansasii that were inhibited within the range of 8 to 250 µM, unsubstituted 4-[(2-hydroxy-benzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide meets the selectivity requirement. In general, dihalogenation of the salicylic moiety improved the antibacterial and antifungal activity but also increased the cytotoxicity, especially with an increasing atomic mass. Some derivatives offer more advantageous properties than the parent sulfadiazine, thus constituting promising hits for further antimicrobial drug development.

Pathogenicity and phenotypic sulfadiazine resistance of Toxoplasma gondii isolates obtained from livestock in northeastern Brazil.

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities.