Determination of fluoroquinolones, sulfonamides, and tetracyclines multiresidues simultaneously in porcine tissue by MSPD and HPLC-DAD

An efficient method is provided to detect simultaneously some important veterinary drugs from different classes in highly complex animal tissue matrix. This method using matrix solid-phase dispersion (MSPD) and high performance liquid chromatography (HPLC) with diode array detection (DAD) is developed to effectively determine two fiuoroquinolones (enoxacin and lomefioxacin), two sulfonamides (sulfanilamide and sulfamethoxazole) and one tetracycline (tetracycline) simultaneously in porcine tissues. In the process, MSPD methodology was used to treat samples, washed by n-hexane to remove lipid, eluted the analytes with acetonitrile–dichloromethane (1:1, v/v). Solvent acetonitrile and solvent acetic acid (0.1%) were combined in a gradient. HPLC–DAD analysis of the tissue samples was performed within 15 min at a fiow rate of 1.0 mL/min. The results showed that a recovery at 0.1, 0.5 and 1.0 mg/g fortification levels ranged from 80.6% to 99.2% with satisfactory relative standard deviations (RSDs) (below 6.1%, nfi3) and the limits of quantitation (LOQ) ranged from 7 mg/kg to 34 mg/kg in porcine tissues. Utilization of the method in successfully simultaneous analysis of porcine tissue incurred with veterinary drug multiresidues is described.

Malaria parasite carbonic anhydrase:inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.

Survey of Tetracyclines, Sulfonamides, Sulfamethazine, and Quinolones in UHT Milk in China Market

This study surveyed 180 samples of ultra high temperature （UHT） milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were 〈1.5, 26.2, 22.6, and 58.8 μg kg-1, respectively. None of the samples exceeded the maximum residue levels （MRLs） for these four veterinary drugs, according to the regulations set by China, the European Union （EU） and the Codex Alimentarius Commission （CAC）.

Study on Pretreatment during Simultaneous Determination of Sulfonamides and Chloramphenicols in Honey

[ Objective] This study was conducted to establish a new UPLC-MS method for simultaneous detection of sulfonanfides and chloramphenicols in honey. [ Method] In this experiment, 0.2% formic acid-acetonitrile was used as an extractant to simultaneously extract chloramphenicoJs and sulfonamides from drugs. The extract was then loaded and extracted with an efficient separation column Oasis PRIME HLB. After nitrogen blow-concentration and dissolution with mobile phase, the extract was loaded on UPLC and detected by MS. [ Resultl There was a good linear relation in the range of 0. 1 - 10 ng/ml for chloramphenicols, with a correlation coefficient of 0.991, while sulfonamides had a good linear relation in the range of 0.5 - 50 ng/ml. The lowest detection limit of chloramphenicols and sulfonamides were 0. 1 and 0.5 μg/kg, respectively. The recoveries were in the range of 82.50% - 101.2%, with RSD values in the range of 3.2% -4.0%. [ Conclusion] This method is simple and fast with low detection limit, high recovery and good reproducibility, and could be used for simultaneous detection of re- sidual chloramphenicols and sulfonamides in honey. Key words UHPLC-MS; Sulfonamides ; Chloramphenicols ; Honey

Study on Rapid Detection of Tetracyclines,Fluoroquinolones and Sulfonamides in Milk

Aiming at the market demand for rapid detection of tetracyclines,fluoroquinolones and sulfonamides in milk,a golloidal gold immunochromatography test strip for simultaneous detection of tetracyclines,fluoroquinolones and sulfonamides in milk was prepared based on the principle of competitive inhibition immunochromatography. The performance indicators of the test strip were verified. The results showed that the test strip can simultaneously detect 4 tetracyclines,13 fluoroquinolones and 13 sulfonamides,and the detection limits all can meet the national residue limits; the tests strip exhibited false positive rate≤5% and false negative rate = 0; and no cross-reaction with other drugs was commonly found in milk,indicating good specificity. The method is simple,rapid,and has low cost and easy popularization. It provides a means for realizing on-site rapid detection and is of important practical significance to guarantee of safety of milk and dairy products in China.

Rational drug design,synthesis,and biological evaluation of novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamides as potential antimalarial,antifungal,and antibacterial agents

Objective Sulfanilamide,sulfadiazine,and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process,which is essential for parasite survival.Therefore,we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.Methods All compounds were synthesized by the conventional method,and the products were characterized by spectral analysis(1 H NMR and mass spectrometry).The progression of the reaction was monitored using thin-layer chromatography(TLC).All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2.Antibacterial and antifungal activities were determined using the broth dilution method.Results S6(N-(2-thiazol-4 yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S9(N-(1 H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds;S8(N-(2-1 H-imidazol-2 yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10(N-(1 H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed four hydrogen bonds with the allosteric site of the enzyme.Considering the docking scores and formation of hydrogen bonds with the target enzyme,the novel derivatives were processed for wet lab synthesis.All the newly synthesized derivatives were subjected to in vitro antimalarial,antifungal,and antibacterial activities.All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards.Moreover,compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities.They also exhibited powerful molecular interactions in molecular docking studies.Conclusion Based on the above results,it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial,antifungal,and antibacterial agents.

New Sulfonamides Derived from Carvacrol: Compounds with High Antibacterial Activity against Resistant Staphylococcus aureus Strains

Nine new sulfonamides derived from carvacrol were prepared through a reaction between 4-hydroxy-2-isopropyl-5-methyl benzene sulfonyl chloride with various amines in excellent yields (76% - 92%). The sulfonamides were characterized using spectrometric and spectroscopic methods. Among these compounds, three derivatives showed excellent results in antibacterial activity against resistant S. aureus strains, with MIC values ranging from 3.9 to 62.50 ppm. The sulfonamide derivative of 4-methylaniline (SULF-1) had the best performance for all tested strains of bacteria (MIC = 3.9 to 15.62 ppm). Furthermore, the sulfonamide derivative of 4-fluoro aniline (SULF-3), which also presented promising results, was found to have a synergistic effect when combined with tetracycline and partial synergistic effect when combined with ampicillin, exhibiting an FIC index between 0.50 and 0.75. The sulfonamide derivative of 4-methylaniline had a synergistic effect in combination with erythromycin exhibiting an FIC index of 0.37. Carvacrol in association with the antibiotics tested did not have a synergistic effect.

Sulfonyl Imidazoles as Reagents for the Preparation of Sulfonates and Sulfonamides

Several new sulfonates and sulfonamides were synthesized with sulfonyl imidazoles as reagents. These compounds were characterized by ^1H NMR. The melting points of all solids synthesized were obtained on Fisher-Johns Melting Point Apparatus.

Simultaneous Prediction of Retention Times and Peak Shapes of Sulfonamides in Reversed-Phase High-Performance Liquid Chromatography

In this paper, we propose a novelmethod based on the plate theory to simultaneously predict retention times and peak shapes under gradient elutions and different flow rates by reversed-phase high-performance liquid chromatography. The proposed method yielded excellent retention prediction results in experiments with 16 common sulfonamides under 18 gradient conditions and four different flow rates, including 0.7, 1.0, 1.3, and 1.5 mL/min. The mean absolute deviation was 0.70%, which indicates accurate prediction. Moreover, the proposed method predicts the change wellin peak shapes caused by the expansion or compression ofpeaks under different gradient conditions.

Design, Synthesis and Characterization of Novel Sulfonamides Derivatives as Anticancer Agent Targeting EGFR TK, and Development of New Methods of Synthesis by Microwave Irradiation

Some novel sulfonamide-derivatives were designed to develop novel kinase inhibitors. The molecular docking study was performed for the designed compounds against epidermal growth factor kinase receptor T790M/L858R (TMLR) (PDB ID: 5EDQ) to identify new drug candidates for treating cancer. Binding free energy was calculated by Molegro virtual docker (MVD) to select the most promising hits. The corresponding docking score values into EGFR (TMLR) of 4b gave the best energy docking -147.213 Kcal/mol. And some of the designed sulfonamide derivatives have been synthesized by conventional method in addition to a microwave-assisted method of synthesis. The reaction of an amino group-containing drug;sulfamethoxazole and sulfanilamide with carbonyl group in benzoyl chloride and phthalic acid in basic media, generated a series of sulfonamide derivatives. The structures of all the synthesized compounds were well characterized by Mass spectrometry (MS), Infrared spectroscopy (IR), 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR) and elemental analysis. After obtaining experimental data regarding the yield and the time taken for the synthesis by both the approaches, conventional and microwave-assisted method, it was shown that the microwave-assisted method gave higher yield with shorter time and higher temperature compared to conventional heating methods.

Effect of Artemisia annua L. as Substitute to Sulfonamides (Sodium Sulfadimerzine) on Coccidiosis and Growth Performance in Rabbits

Coccidiosis is a disease caused by protozoa of the genus Eimeria which seriously affects young rabbits. Treatment based on the use of anticoccidial drugs is increasingly ineffective due to the rapid emergence of resistant strains of coccidia and the high cost of drugs. Consumer demand for rabbit products without chemical residues led to a growing interest in the use of medicinal plants as an alternative treatment for coccidiosis. The present study was carried out during the period of August to December 2020 to assess the anticoccidial effect of hydro-ethanolic extract of leaves of Artemisia annua L., in young rabbits. The antiparasitic efficacy of Artemisia extract was tested on 15 young rabbits (whose age varied between 7 and 9 weeks) divided into 5 lots of 3 animals. The average weight of these animals was 790 g. The results of this study show that the feces samples and the weight of young rabbits before administration of the treatment and the coprological examination (every 7 days for 4 weeks) show a fecal excretion reduction rate (FECRT) of 55.13% in the lot treated by sulfonamide. On the other hand, in animals received treatments extract of the leaves of Artemisia annua L., the average FECRT is evaluated at 69.64%, 79.22%, and 96.36% for respective doses of 400, 800 and 1200 mg/kg bodyweight and proves their anticoccidial effect. Furthermore, the variation in mean Eggs Per Gram (EPG) of coccidia and the average weekly weight gain (AWWG) of each lot were significant in the lots treated with hydro-ethanolic extract (P 0.05). The greatest reductions in oocystal excretion and weight gain obtained were those of lot 5, treated at 1200 mg/kg of hydro-ethanolic leaves extract of Artemisia annua L.

Structural effects of sulfonamides on the proliferation dynamics of sulfonamide resistance genes in the sequencing batch reactors and the mechanism

Antibiotic resistance genes(ARGs)can be easily promoted by antibiotics,however,the structural effects of antibiotics on the proliferation of ARGs dynamic and the associated mechanisms remain obscure in,especially,activated sludge sequencing batch reactors.In the present study,the effects of 9 sulfonamides(SAs)with different structures on the proliferation dynamic of sulfonamide resistance genes(Suls)in the activated sludge sequencing batch reactors and the corresponding mechanisms were determined(30 days),and the results showed that the largest proliferation value(ΔA^(R))of Suls dynamic for SAs(sulfachloropyridazine)was approximately 2.9 times than that of the smallest one(sulfadiazine).The proliferation of Suls was significantly related to the structural features(minHBint6,SssNH,SHBd and SpMax2_Bhm)that represent the biological activity of SAs.To interpret the phenomenon,a mechanistic model was developed and the results indicated that the biodegradation of SAs(T_(1/2))rather than conjugative transfer frequency or mutation frequency tends to be the key process for affecting Suls proliferation.T_(1/2)was proved to be dependent on the interactions between SAs and receptors(E_(binding)),the cleavage mode(bond dissociation energy),and the site of nucleophilic assault.Besides,the metagenomic analysis showed that SAs posed significant effect on antibiotic resistome and Tnp31 played a vital role in the proliferation of Suls.Overall,our findings provide important insight into a theoretical basis for understanding the structural effects of SAs on the proliferation of ARGs in SBR systems.

Electrochemical Dearomative Spirocyclization of N-Acyl Sulfonamides in a Continuous-Flow Cell

The development of efficient and sustainable methods to obtain spirocyclic compounds is of significance as these structures are widely found in pharmaceuticals and agrochemicals.Herein,we disclose an electrochemical dearomative spirocyclization of N-acyl sulfonamides in a continuous-flow cell.The reaction is simple and efficient without external catalysts or supporting electrolytes and could be applied in a decagram-scale synthesis.

Gold immunochromatographic sensor for the rapid detection of twenty-six sulfonamides in foods

A gold immunochromatographic sensor （GICS） was developed for the rapid detection of 26 sulfonamides in honey samples. The sensor was based on a group-specific monoclonal antibody （mAb） that can recognize all 26 sulfonamides. Three haptens （hapten I with a thiazole ring, hapten 2 with a benzene ring, and hapten 3 with a straight carbon chain） were used for antigen preparation. With hybridoma technology, a group-specific mAb was screened with a 50% maximal inhibitory concentration （IC50） against sulfathizole （STZ） and the other 25 analogues ranging from 0.08 to 90.18 ng/mL. Mono-dispersed gold nanoparticles were conjugated with the mAb to develop the lateral immunochromatographic strip. A labeled antibody concentration of 0.1 pg/mL and a coating antigen concentration of 0.2 μg/mL in the test line were chosen for strip preparation. Under optimized conditions, the visual limits of detection （vLOD） for the concentrations of STZ, sulfamethoxazole, sulfamethizole, sulfadiazine, sulfamerazine, sulfadimethoxine, sulfamonomethoxine, sulfameter, sulfamethoxypyridazine, and sulfachloropyridazine were 5, 0.25, 0.25, 10, 5, 10, 25, 2.5, 5, 0.25, and 10 μg/kg, respectively. Scanner analysis in honey samples revealed good performance for detection of the 26 sulfonamides. Commercial honey samples were tested with the sensor and positive results were confirmed with high-performance liquid chromatography. The proposed strip sensor provides a convenient method for the rapid and reliable determination of sulfonamides pollutants in honey samples.

Adsorption of sulfonamides on lake sediments

Sulfonamides （SAs） are one class of the most widely used antibiotics around the world. Their fate and transport in the aquatic environment is of great concern. In this study, adsorption of four SAs--sulfadiazine （SD）, sulfamethoxazole （SMZ）, sulfadimethoxine （SDM） and sulfamethazine （SM2）---in single-solute and multi-solute systems on sediments of Dianchi （DC） Lake and Taihu （TH） Lake, China was investigated with batch experi- ments. In the single-solute adsorption system, the Langmuir model and the dual-mode model described the adsorption process better than the Freundlich model. Model fitness was better on DC sediment than on TH sediment. The order of adsorption capacity approximately followed a decreasing order of SDM ~ SD 〉 SM2 〉 SMZ on both sediments, which was likely attributed to the distinctly different water solubility of the four SAs. In the multi-solute system, the order of adsorption capacity was SM2 〉 SDM 〉 SD 〉 SMZ, which was probably related to the compound speciation caused by the pH values of the experimental solution. In the multi-solute system, both competitive and cooperative adsorption played important roles in the adsorption of sulfonamides on sediments.

Rhodium-catalyzed aerobic N-alkylation of sulfonamides with alcohols

By using the famous Wilkinson＇s catalyst, N-alkylation of sulfonamides can be easily realized under mild aerobic conditions by using alcohols as the alkylating reagent, giving monoalkylated sulfonamides in high yields and selectivities with water produced as the only byproduct. This advantageous aerobic method is potentially general in substrate scope that it can also be applied to other amides, amines and alcohols.

Synergistic sulfonamides plus clindamycin as an alternative therapeutic regimen for HIV-associated Toxoplasma encephalitis: a randomized controlled trial

Background: The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.Methods: This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.Results: A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen Avs. 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3 % (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44]vs. 70.2% [33/47],P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.Conclusions: Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.Trial Registration: ChiCTR.org.cn, ChiCTR1900021195.

An efficient and facile synthesis of N-Cbz-β-aminoalkanesulfonamides

An efficient method for the synthesis of N-Cbz-β-aminoalkanesulfonamides was described.N-Cbz-β-aminoalkanesulfonamides were readily prepared in good yields from a variety of amino alcohols,including optically active ones,via N-Cbz protection with benzyl chloroformate,Mitsunobu esterification reaction with thiolacetic acid,N-chlorosuccinimide oxidation,and ammonolysis process.

Magnetic Ti_(3)C_(2)T_(x)/Fe_(3)O_(4)/Ag substrate for rapid quantification of trace sulfonamides in aquatic products by surface enhanced Raman spectroscopy

Surface-enhanced Raman scattering(SERS)spectroscopy has been employed as a rapid analysis technology for food security inspection recently.Nowadays,it is still a great challenge to rapidly quantify multiple trace antibiotics potentially abused in aquaculture industry.In this work,a magnetic Ti_(3)C_(2)T_(x)/Fe_(3)O_(4)/Ag substrate was prepared for the development of a reliable rapid SERS quantification method for multiple trace sulfonamides in aquatic products.This magnetic substrate had good uniformity,reproducibility,stability and SERS activity.Moreover,this substrate could integrate the magnetic separation-enrichment and matrix clean-up without cross contamination,which endowed it with good selectivity and antiinterference capability during real sample analysis.The electromagnetic enhancement and chemical enhancement mechanism of this magnetic substrate were studied in detail to reveal its good separationenrichment performance and SERS activity.Finally,a rapid SERS quantification method was established and practically applied for trace phthalic sulfathiazole(PST)and silver sulfadiazine(SSD)in aquatic products by using Ti_(3)C_(2)T_(x)/Fe_(3)O_(4)/Ag magnetic substrates.Trace PST and SSD could be actually detected and quantified as 55.9μg/kg and 64.0μg/kg in aquatic products,respectively.Good recoveries of 83.9%-116%with relative standard deviations(RSDs)of 0.5%-3.2%for PST and 80.2%-102%with RSDs of 1.3%-5.8%for SSD were obtained.This work proposed an efficient and reliable method for rapid quantification of trace multiple sulfonamides in complex aquatic samples during food security inspection.

Biochemical responses of the freshwater microalga Dictyosphaerium sp. upon exposure to three sulfonamides

Sulfonamides(SAs)are common antimicrobial drugs,which are frequently detected in surface water systems,and are difficult to degrade,posing a potential threat to the aquatic environment.However,little is known about the potential adverse effects of SAs on nontarget organisms(e.g.,microalgae)in the aquatic ecosystem.In this study,the effect of SAs(sulfadiazine(SD),sulfamerazine(SM1),and sulfamethazine(SM2)at 1,5,20,and 50 mg/L concentrations,respectively)on the freshwater microalga Dictyosphaerium sp.was investigated,with respect to changes of biomass and chlorophyll a content and induction of extracellular polymer substances(EPS),including protein and polysaccharide contents.At the same time,the residue of SAs was determined.The results showed that Dictyosphaerium sp.was tolerant to the three SAs,and the chlorophyll a content in Dictyosphaerium sp.significantly decreased on day 7,followed by a"compensation phenomena".The increase in protein and polysaccharide contents played a defensive role in Dictyosphaerium sp.against antibiotic stress,and there was a strong positive correlation between polysaccharide contents and antibiotic concentrations.Dictyosphaerium sp.exhibited 35%–45%,30%–42%,and 26%–51%removal of SD,SM1,and SM2,respectively.This study is helpful to understand the changes of EPS in the defense process of microalgae under the action of antibiotics,and provides a new insight for the ecological removal of antibiotic pollution in natural surface water system.