Bioinspired pH- and Temperature-Responsive Injectable Adhesive Hydrogels with Polyplexes Promotes Skin Wound Healing.

Despite great potential, the delivery of genetic materials into cells or tissues of interest remains challenging owing to their susceptibility to nuclease degradation, lack of permeability to the cell membrane, and short in vivo half-life, which severely restrict their widespread use in therapeutics. To surmount these shortcomings, we developed a bioinspired in situ-forming pH- and temperature-sensitive injectable hydrogel depot that could control the delivery of DNA-bearing polyplexes for versatile biomedical applications. A series of multiblock copolymer, comprised of water-soluble poly(ethylene glycol) (PEG) and pH- and temperature-responsive poly(sulfamethazine ester urethane) (PSMEU), has been synthesized as in situ-forming injectable hydrogelators. The free-flowing PEG-PSMEU copolymer sols at high pH and room temperature (pH 8.5, 23 °C) were transformed to stable gel at the body condition (pH 7.4, 37 °C). Physical and mechanical properties of hydrogels, including their degradation rate and viscosity, are elegantly controlled by varying the composition of urethane ester units. Subcutaneous administration of free-flowing PEG-PSMEU copolymer sols to the dorsal region of Sprague-Dawley rats instantly formed hydrogel depot. The degradation of the hydrogel depot was slow at the beginning and found to be bioresorbable after two months. Cationic protein or DNA-bearing polyplex-loaded PEG-PSMEU copolymer sols formed stable gel and controlled its release over 10 days in vivo. Owing to the presence of urethane linkages, the PEG-PSMEU possesses excellent adhesion strength to wide range of surfaces including glass, plastic, and fresh organs. More importantly, the hydrogels effectively adhered on human skin and peeled easily without eliciting an inflammatory response. Subcutaneous implantation of PEG-PSMEU copolymer sols effectively sealed the ruptured skin, which accelerated the wound healing process as observed by the skin appendage morphogenesis. The bioinspired in situ-forming pH- and temperature-sensitive injectable adhesive hydrogel may provide a promising platform for myriad biomedical applications as controlled delivery vehicle, adhesive, and tissue regeneration.

The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine.

Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group-specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non-compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within-drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P-value<0.05; Cl, Vdss ) and oxfendazole (P-value<0.05, AUC0→∞ ). Sex differences existed for oxfendazole (P-value < 0.05; Tmax ) and sulfamethazine (P-value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population.

Biodegradation studies of N4-acetylsulfapyridine and N4-acetylsulfamethazine in environmental water by applying mass spectrometry techniques.

This work evaluates the biodegradation of N(4)-acetylsulfapyridine (AcSPY) and N(4)-acetylsulfamethazine (AcSMZ), metabolites of two of the most commonly used sulfonamides (SAs) in human and veterinary medicine, respectively. Aerobic transformation in effluent wastewater was simulated using aerated fixed-bed bioreactors. No visible changes in concentration were observed in the AcSMZ reactor after 90 days, whereas AcSPY was fully degraded after 32 days of experiment. It was also demonstrated that AcSPY transformed back to its parent compound sulfapyridine (SPY). The environmental presence of these two metabolites in wastewater effluent had been previously investigated and confirmed, together with three more SA acetylated metabolites and their corresponding parent compounds, in 18 different wastewater treatment plants in Hesse (Germany). Sulfamethoxazole (SMX) and SPY were the two SAs detected most frequently (90% and 89% of the samples, respectively) and in the highest concentrations (682 ng L(-1) for SMX and 532 ng L(-1) for SPY). To conclude, hazard quotients were calculated whenever toxicity data were available. None of the SAs studied posed an environmental risk.

Residue accumulation, distribution, and withdrawal period of sulfamethazine and N-acetylsulfamethazine in poultry waste from broilers.

Sulfamethazine is one of the most frequently used sulfonamides in the poultry farming industry. However, the residue accumulation, distribution, and depletion of sulfamethazine (SMZ) and its metabolite, N4-acetylsulfamethazine (NAS), in poultry waste (manure and feathers) have yet to be evaluated. In our study, the residue levels of SMZ and NAS in manure and feathers are determined by liquid chromatography tandem mass spectrometry. Furthermore, the distribution, depletion, and withdrawal period of SMZ and NAS in manure and feathers are investigated under field conditions. Results show that high concentrations (0.7-43.3 mg/kg for SMZ, and 0.22-22.4 mg/kg for NAS) of SMZ and NAS residues remain in manure and feathers even when SMZ has been used. The withdrawal periods of SMZ and NAS in feathers are 97.0 d and 28.0 d, respectively. In manure, the withdrawal period is 18.2 d and 8.0 d, respectively. Poultry waste is a possible major reentry way of SMZ into the food chain and the environment.

Antibacterial and molecular docking studies of newly synthesized nucleosides and Schiff bases derived from sulfadimidines.

A new series of nucleosides, moieties, and Schiff bases were synthesized from sulfadimidine. Infrared (IR), 1HNMR, 13C NMR, and mass spectrometry techniques and elemental analysis were employed to elucidate the synthesized compounds. The prepared analogues were purified by different chromatographic techniques (preparative TLC and column chromatography). Molecular docking studies of synthesized compounds 3a, 4b, 6a, and 6e demonstrated the binding mode involved in the active site of DNA gyrase. Finally, all synthesized compounds were tested against selected bacterial strains. The most effective synthesized compounds against S. aureus were 3a, 4d, 4b, 3b, 3c, 4c, and 6f, which exhibited inhibition zones of inhibition of 24.33 ± 1.528, 24.67 ± 0.577, 23.67 ± 0.577, 22.33 ± 1.528, 18.67 ± 1.528 and 19.33 ± 0.577, respectively. Notably, the smallest zones were observed for 4a, 6d, 6e and 6g (6.33 ± 1.528, 11.33 ± 1.528, 11.67 ± 1.528 and 14.66 ± 1.155, respectively). Finally, 6b and 6c gave negative zone values. K. pneumoniae was treated with the same compounds and the following results were obtained. The most effective compounds were 4d, 4c, 4b and 3c, which showed inhibition zones of 29.67 ± 1.528, 24.67 ± 0.577, 23.67 ± 1.155 and 19.33 ± 1.528, respectively, followed by 4a and 3d (15.33 ± 1.528 for both), while moderate results (13.67 ± 1.155 and 11.33 ± 1.528) were obtained for 6f and 6g, respectively. Finally, 6a, 6b, 6c, 3a, and 3b did not show any inhibition. The most effective compounds observed for the treatment of E. coli were 4d, 4b, 4c, 3d, 6e and 6f (inhibition zones of 26.33 ± 0.577, 21.67 ± 1.528, 21.67 ± 1.528, 19.67 ± 1.528, 17.67 ± 1.155 and 16.67 ± 1.155, respectively). Compounds 3b, 3c, 6a, 6c, and 6g gave moderate results (13.67 ± 1.528, 12.67 ± 1.528, 11.33 ± 0.577, 15.33 ± 1.528 and 12.67 ± 1.528, respectively), while 6b showed no effect. The MIC values against S. aureus ranged from 50 to 3.125 mg, while those against E. coli and K. pneumoniae ranged from 50 to 1562 mg. In vitro, the antibacterial effects were promising. Further research is required to study the in vivo antibacterial effects of these compounds and determine therapeutic doses.

Sulphamethazine derivatives as immunomodulating agents: New therapeutic strategies for inflammatory diseases.

Sulfamethazine (SMZ) (1) is an antibacterial sulfa drug which suppresses the synthesis of dihydrofolic acid. It is used for the treatment of infections in livestock; such as gastrointestinal, and respiratory tract infections. During the current study, synthesis, characterization, and evaluation of immunomodulatory activities of derivatives of sulfamethazine (SMZ) (3-39) was carried out. These derivatives were synthesized by the reaction of sulfamethazine with a range of acid chlorides. All the compounds were characterized by using modern spectroscopic techniques, such as 1H-, and 13C-NMR, EI-MS, and HRFAB-MS. Compounds 3-10, 14, and 15 were identified as new compounds. Immunomodulatory effect of compounds 3-39 on different parameters of innate immune response was evaluated, including the production of Reactive Oxygen Species (ROS) from human whole blood and isolated polymorphonuclear neutrophils (PMNs), nitric oxide (NO), and pro-inflammatory cytokine TNF-α. All the new compounds, except 14 and 15, showed a significant anti-inflammatory activity. Compounds 3-39 were also evaluated for their anti-bacterial activity and cytotoxicity (3T3 mouse fibroblast cell lines). All the compounds were found to be non-cytotoxic against normal cell lines.

Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse.

The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli.

Absorption of N4-D-glucopyranosylsulphamethazine by rat everted intestinal sacs.

Absorption of the N4-D-glucose conjugate of sulphamethazine (glucose-SMZ, 0.5 mM) by isolated everted sacs of the rat small intestine was studied at 37 degrees and pH 6.6. Phlorizin (0.5-2.0 mM) significantly reduced (P < 0.05) both mucosal and serosal transfer of glucose-SMZ and inhibition of mucosal transfer appeared to be concentration-dependent. Phloretin (0.5 mM) and removal of Na+ from the incubation medium also diminished absorption of glucose-SMZ. Furthermore, D-glucose (0.5 and 5.0 mM) inhibited mucosal and serosal transfer of the glycoside. The results suggest the D-glucose/Na+ cotransporter mediates absorption of glucose-SMZ from the small intestine of the rat. Thus, glucose-SMZ might be bioavailable from ingested tissues in which it is present.

Facile separation of sulfonamides from their degradates by liquid--liquid extraction.

Regulation of acidity for protonation of the free N4-amine can provide for the selective liquid--liquid extraction isolation of a sulfonamide from its degradation products. This principle is applied for the stability-indicating determination of sulfacetamide in the presence of sulfanilamide, sulfaquinoxaline in feed, and sulfabromomethazine in dosage forms. In solution, sulfabromomethazine can exhibit photodecomposition to sulfamethazine. The mean relative errors of the these methods and the precision, represented by relative standard deviations, are each typically less than 2%.

Synthesis and anti-HIV activity of 4-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene) amino]-N(4,6-dimethyl-2-pyrimidinyl)-benzene sulfonamide and its derivatives.

4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene) amino]-N(4,6-dimethyl-2-pyrimidinyl)-benzene sulphonamide and its derivatives were synthesized by reaction of isatin and its derivatives with sulphadimidine. Their chemical structures have been confirmed by IR, (1)H NMR data and elemental analysis. Investigation of anti-HIV activity of compounds were tested against replication of HIV-1 (IIIB) and HIV-2 (ROD) strains in acutely infected MT-4 cells and the activity compared with standard azidothymidine. Among the compounds tested, 4-[(1,2-dihydro-2 oxo-3H-indol-3-ylidene)amino]-N(4,6-dimethyl-2-pyrimidinyl)-benzene sulphonamide and its N-acetyl derivative were the most active compounds.

A sensitive method for detection of sulfamethazine and N4-acetylsulfamethazine residues in environmental samples using solid phase immunoextraction coupled with MALDI-TOF MS.

Sulfamethazine (SMT) and its major metabolite, N(4)-acetylsulfamethazine (NA-SMT), were each recovered from spiked water (0.1 ppb) and 10% (w/v) aqueous suspensions of soil (1 ppb) or composted manure (1 ppb), by using a three-stage solid phase immunoextraction (SPIE) system, followed by detection with matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Sulfonamide recovery rates are reported for separate stages of the SPIE system and for trace-level sulfonamide SPIE extraction from the environmental samples. SPIE MALDI-TOF MS is a rapid and definitive technique with potentially better efficiency relative to other established trace-level sulfonamide analytical methods. SPIE MALDI-TOF MS required 1.5 h per batch (8-24 samples/batch) for sample enrichment, 5 min per batch for probe preparation, and 5 min per sample to acquire and process the spectrum. This is the first time MALDI-TOF MS has been reported as a potential means of detecting trace-level drug residues in complex environmental samples.

The effect of moderate haemodilution with Fluosol-DA or Hespan on the nonmicrosomal acetylation of sulphadimidine in the rat.

The effects of Fluosol-DA (Fluosol) and Hespan haemodilution on the nonmicrosomal acetylation of sulphadimidine were studied in male rats. Fluosol increased the acetylsulphadimidine percent excreted in urine, the metabolic formation rate constant (kf), and the formation clearance (CLF) for 72 h after haemodilution without any significant changes in the sulphadimidine apparent volume of distribution (Vd) or total body clearance (CL). Hespan haemodilution increased the acetylsulphadimidine percent excreted in urine only at 48 h while significantly decreasing the sulphadimidine clearance, urinary excretion rate constant (ku), and renal clearance (CLR) for 72 h. The enhanced N-acetyltransferase activity after Fluosol haemodilution may have therapeutic consequences for concomitantly given drugs metabolized by this enzyme.

Practical screening procedures for sulfamethazine and N4-acetylsulfamethazine in milk at low parts-per-billion levels.

Relatively simple and inexpensive procedures for screening milk for sulfamethazine (SMZ) and one of its metabolites, N4-acetylsulfamethazine (ASMZ), are detailed. Both methods detect at the low parts-per-billion level and are suitable for both field and laboratory use. Milk is passed over Chromosorb 102, which adsorbs SMZ. The drug is eluted and purified by direct passage of the effluent over small beds of buffered anion-exchange resins and alumina and is finally isolated and detected colorimetrically. For ASMZ, the procedure is modified so that SMZ is removed in the purification steps. The isolated ASMZ is then hydrolyzed to SMZ for detection. Application of the methods 5 years apart (1988 and 1993) shows that SMZ is still being used but to a lesser extent in 1993. Of over 250 samples screened in the 2 studies, only 2 were estimated to contain SMZ at 10 ppb, and the majority contained SMZ at 1 ppb. ASMZ was detected in a number of samples that were negative for SMZ.

Age and dosage dependency in the plasma disposition and the renal clearance of sulfamethazine and its N4-acetyl and hydroxy metabolites in calves and cows.

Plasma disposition, protein binding, urinary recovery, and renal clearance of sulfamethazine (SMZ), its N4-acetylsulfamethazine (N4-SMZ), and its 2 hydroxy metabolites--6-hydroxymethylsulfamethazine (SCH2OH) and 5-hydroxysulfamethazine (SOL)--and the glucuronide of the latter were studied in 7 cows and 7 calves to determine the relationship between these values and the age of the animal and dosage applied. A capacity-limited hydroxylation of SMZ into SCH2OH was observed in cows and calves given dosages of 100 to 200 mg/kg. A biphasic SMZ elimination curve and steady state in SCH2OH plasma concentration (6 to 15 micrograms/ml) were observed. The N4-SMZ plasma concentration-time curve was parallel to that of SMZ at the dosages and in all animals. The total body clearance and the cumulative urinary recovery (expressed as percentage of the dose) for SMZ and its metabolites depended on drug dosage and age of the animals. At dosages of SMZ less than 25 mg/kg, the main metabolite in the urine of calves and cows was SCH2OH (23% to 55.2%), whereas in calves given a larger dosage (100 mg/kg), the N4-SMZ and SOH percentages increased. The plasma protein binding of SMZ and its metabolites depended on the SMZ plasma concentration. Hydroxylation lowered the protein binding (from 75-80%) to 50%. The renal clearance of SMZ was dependent on urine flow in all animals. The renal clearance of the SCH2OH metabolite was 2 to 3 times greater than the creatinine clearance value; thus, this compound was excreted by glomerular filtration and partly by tubular secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics, metabolism, and renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy metabolites in calves and cows.

The effect of molecular structure on the drug disposition and protein binding in plasma and milk, the urinary recovery, and the renal clearance of sulfadiazine, sulfamerazine, and sulfamethazine and of their N4-acetyl and hydroxy derivatives were studied in calves and cows. Sulfadiazine was highly acetylated and was slightly hydroxylated. Sulfamerazine and sulfamethazine were hydroxylated predominantly at the methyl group of the pyrimidine side chain; hydroxylation of the pyrimidine ring itself was more extensive for sulfamethazine than for sulfamerazine. At dosages between 100 and 200 mg/kg of body weight, sulfamethazine had a capacity-limited elimination pattern, which was not observed for sulfadiazine or sulfamerazine. The concentrations of the parent sulfonamide and its metabolites in plasma and milk were parallel, the latter being lower. Metabolite concentrations in milk were at least 8 times lower than those of the parent drug. Metabolism speeds drug elimination, producing compounds with renal clearance values higher than those of the parent drug. The effect on the metabolism and renal clearance of methyl substitution in the pyrimidine side chain is discussed.

Pharmacokinetics, renal clearance, tissue distribution, and residue aspects of sulphadimidine and its N4-acetyl metabolite in pigs.

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.

Dose dependent disposition of sulphadimidine and of its N4-acetyl and hydroxy metabolites in plasma and milk of dairy cows.

The disposition of sulphadimidine (SDM) and of its N4-acetyl (N4-SDM) and two hydroxy metabolites, 6-hydroxymethyl-(SCH2OH) and 5-hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine-33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH2OH. The metabolite percentages, the final plasma elimination half-lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond 4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk. At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 micrograms/ml, a capacity limited metabolism of SDM to SCH2OH was noticed, viz. a steady state concentration of SCH2OH and a biphasic elimination pattern for SDM and SCH2OH in plasma and milk. The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH2OH, SOH, and N4-SDM were: 0.69, 0.22, 020, and 0.63, respectively. The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose. A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 micrograms/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.

Pharmacokinetics and renal clearance of sulphadimidine, sulphamerazine and sulphadiazine and their N4-acetyl and hydroxy metabolites in pigs.

The effect of molecular structure on the drug disposition and protein binding in plasma, the urinary recovery, and the renal clearance of sulphamerazine (SMR), sulphadiazine (SDZ), and sulphadimidine (SDM) and their N4-acetyl and hydroxy derivatives were studied in pigs. Following IV administration of SDM, SMR and SDZ, their mean elimination half-lives were 12.4 h, 4.3 h and 4.9 h respectively. The plasma concentrations of parent sulphonamide were higher than those of the metabolites, and ran parallel. The acetylated derivatives were the main metabolites; traces of 6-hydroxymethylsulphamerazine and 4-hydroxysulphadiazine were detected in plasma. The urine recovery data showed that in pigs acetylation is the major elimination pathway of SDM, SMR and SDZ; hydroxylation became more important in case of SMR (6-hydroxymethyl and 4-hydroxy derivatives) and SDZ (4-hydroxy derivatives) than in SDM. In pigs methyl substitution of the pyrimidine side chain decreased the renal clearance of the parent drug and made the parent compound less accessible for hydroxylation. Acetylation and hydroxylation speeded up drug elimination, because their renal clearance values were higher than those of the parent drug.

Tissue residues of some sulphonamides in normal and Eimeria stiedai infected rabbits.

Tissue residues of sulphadiazine (SDZ), sulphadimidine (SDD) and sulphquinoxaline (SQ) were studied in healthy and E. stiedai infected rabbits following oral administration of 0.5 g/l drinking water for 5 days. The solid-phase extraction and HPLC was used to determine the concentration of the three sulphonamides in a single tissue sample. SDZ was detected in the liver and kidney in concentrations below the tolerance levels at day 5 and no residues could be detected at day 7 after drug withdrawal. SDD and SQ were detected in all of the tested organs of healthy rabbits up to day 5, where the highest concentration was reported in the liver (0.08 +/- 0.02 and 0.09 +/- 0.02 g/g respectively). In infected rabbits, the three sulphonamides were detected up to day 7 in concentrations higher than the tolerance limits (> 0.1 g/g) in the liver and kidney and lower levels in other tissues. A withdrawal period of 4 days for SDZ and 5 days for SDD and SQ in healthy rabbits and 7 days for SDZ and 8 days for SDD and SQ in E. stiedai infected rabbits is suggested.

Sulfa drugs as inhibitors of carbonic anhydrase: new targets for the old drugs.

Sulfa drugs are well-known antibacterial agents containing N-substituted sulfonamide group on para position of aniline ring (NH2RSO2NHR'). In this study 2,4-dichloro-1,3,5-triazine derivatives of sulfa drugs, sulfamerazine (1b), sulfaquinoxaline (2b), sulfadiazine (3b), sulfadimidine (4b), and sulfachloropyrazine (5b) (1a-5a) were synthesized and characterized. Their carbonic anhydrase inhibition activity was evaluated against bovine cytosolic carbonic anhydrase isozyme II (bCA II). For the sake of comparison the CA inhibition activity of the parent sulfa drugs (1b-5b) was also evaluated. A significant increase in CA inhibition activity of sulfa drugs was observed upon substitution with 2,4-dichloro-1,3,5-triazine moiety. Molecular docking studies were carried out to highlight binding site interactions. ADME properties were calculated to evaluate drug likeness of the compounds.