Sulfonamide Research Articles

Solution stage fluorescence and anticancer properties of azomethine compounds from sulpha drugs: Synthesis, experimental and theoretical insights

In this comprehensive scientific study, we present the synthesis, characterization, and detailed analysis of two Schiff base compounds, (E)-4-((4-bromobenzylidene)amino)-N-(thiazole-2-yl)benzenesulfonamide (4BRTH) and (E)-4-((1-phenylethylidene)amino)-N-(thiazole-2-yl)benzenesulfonamide (APTH). These Schiff bases were synthesized from sulfathiazole, 4-bromobenzaldehyde, and acetophenone, employing acid-catalyzed reactions. The compounds were characterized using spectroscopic techniques, including UV, IR, and NMR. Notably, the UV spectra revealed absorption peaks at 295, 328, and 345 nm for 4BRTH and 270, 295, and 325 nm for APTH, with calculated oscillator strengths of 0.497, 0.3637, and 0.4138 for 4BRTH and 0.4841, 0.0005, and 0.1247 for APTH. Furthermore, fluorescence studies indicated unique emission peaks at 401 and 706 nm for 4BRTH and 412 and 725 nm for APTH, with excitation wavelengths at 297 nm for 4BRTH and 289 nm for APTH. The compounds displayed fluorescence characteristics, further showcasing their potential as fluorescent probes. Computational simulations were performed using various theoretical levels, including DFT calculations with the B3LYP functional and cc-pVDZ basis sets. The HOMO-LUMO gap was found to be 1.83 eV for 4BRTH and 2.04 eV for APTH, suggesting their reactivity towards other molecules. Theoretical binding energies from molecular docking studies against the breast cancer-related protein 6NLV revealed binding affinities of -18.63 kcal/mol for 4BRTH and -19.84 kcal/mol for APTH, providing insights into their potential anti-cancer activity. Moreover, in vitro anti-cancer assays conducted on MCF7 breast cancer cells demonstrated that both compounds exhibited anti-cancer activity with IC50 values. Importantly, the IC50 values were within the range of the standard anti-cancer drug cisplatin, which had an IC50 value of 62.5 μg/mL. These findings underscore the potential of 4BRTH and APTH as candidates for further anti-cancer drug development.

Synthesis of N-Acylsulfonamide Derivates: New Sulfa Drug Analogues by Sulfo-Click Reaction

Synthesis of N-Acylsulfonamide Derivates: New Sulfa Drug Analogues by Sulfo-Click Reaction

One-pot preparation of magnetic molecularly imprinted adsorbent with dual template molecules for simultaneously specific capture of sulfonamides and quinolones in water and milk samples

Specific capture is a beneficial tactic in simultaneous monitoring of sulfonamides (SAs) and quinolones (QLs). For this purpose, a new magnetic molecularly imprinted adsorbent based on double-template molecules (DT-MIP@MNA) was facilely prepared by “one-pot” hydrothermal technique and utilized as the adsorbent of magnetic solid-phase extraction (MSPE). Molecular simulation technique was employed to quickly screen functional monomer. The recognition factors of prepared adsorbent towards templates sulfamethazine and nalidixic acid were 5.89 and 2.90, respectively, and the corresponding adsorption capacities were as high as 8.85 mg/g and 8.97 mg/g, respectively. Under the optimized parameters, the proposed DT-MIP@MNA/MSPE was combined with HPLC to simultaneously and selectively monitor trace SAs and QLs residuals in water and milk samples. The achieved limits of detection were 0.012–0.028 μg/L and 0.015–0.032 μg/kg for water and milk samples, respectively. The current supplied a sensitive, reliable and anti-interference method for simultaneously monitoring trace SAs and QLs in food.

Source Apportionment and Source-specific Risk of Typical Antibiotics in Baiyangdian Lake

The current situation of antibiotic pollution in lakes is critical. At present, most of the previous studies on antibiotics in lakes have focused on the spatiotemporal distribution and risk assessment, while less attention has been paid to the source apportionment. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of tetracyclines (TCs), sulfonamides (SAs), and quinolones (QNs) in the samples. The source apportionment and source-specific risk of typical antibiotics in the study area were analyzed using the combination of a PMF model and risk quotients (RQ). The results showed that ① the total concentrations of target antibiotics (Σ antibiotics) ranged from ND to 2635 ng·L-1 for surface water and from ND to 259.8 ng·g-1 for sediments. ② The spatial distribution of QNs in surface water decreased from west to east, SAs decreased from middle to north and south, and TCs increased from middle to north and south. In the sediment, QNs decreased from middle to east and west, whereas SAs and TCs increased from east to west. ③ Aquaculture was the major antibiotic source, accounting for the highest proportion (33.2%), followed by sewage treatment plants (29.2%), livestock activities (18.9%), and domestic sewage (18.7%). ④ The ecological risk assessment results showed that enrofloxacin and flumequine were at a medium-high risk level. ⑤ For the spatial distribution of source-specific risk, the results showed that the aquaculture at S1 was at a high risk level, whereas the source-specific risks for other sites were at a medium-low risk level. In terms of source types, aquaculture was at a medium-high risk level, whereas the other sources were at a medium-low risk level. Therefore, considering the major sources and source-specific risk level of antibiotics, more precise and scientific antibiotic risk control should be adopted in Baiyangdian Lake.

The effect of sulfadiazine in manure on accumulation of sulfonamide resistance genes in freshly consumable plants

BackgroundAntibiotic resistance genes will spread via soil fertilized with animal manure to food products. Especially plants whose harvested products can be consumed freshly are of concern. The aim of this study was to assess the impact of sulfadiazine (SDZ)-manured soil on the occurrence of sulfonamide (SA) resistance genes in freshly consumable plants.MethodsSulfadiazine-containing manure was administered via soil to lettuce and leek plants. At harvest, the rhizosphere soil, roots and leaves were investigated on the presence of SDZ-resistant bacteria and sul1 and sul2 genes via qPCR. Further, the impact of SDZ in manure on bacterial community and antibiotic resistance gene composition via amplicon sequencing and shotgun metagenomics was investigated in rhizosphere soils.ResultsAmendment of SDZ to manure resulted in an increase in sul2 genes in manure. However, abundances of sul genes in rhizosphere soils was strongly determined by plant growth and not by soil treatments with SDZ-manure, which was also the case for the bacterial community composition. Effects of SDZ at low or undetectable levels in leek rhizosphere soil became evident by bacterial association network and resistome analyses, and also in roots and leaves by SDZ-selective bacterial cultivation.ConclusionsAntibiotic residues present in animal manure can lead to an increase in antibiotic resistances in food products. Plants play an important role in selection of antibiotic resistance genes present in manured soil. Transmission of antibiotic resistances via manure to the soil–plant ecosystem must be placed into the context of soils as vast reservoirs of ARGs.

Interactions between sulfonamide homologues and glycosyltransferase induced metabolic disorders in rice (Oryza sativa L.)

Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle structural differences. This study conducted an in-depth investigation on the interactions between SA homologues, i.e. sulfadiazine (SD), sulfamerazine (SD1), and sulfamethazine (SD2), and the key metabolic enzyme (glycosyltransferase, GT) in rice (Oryza sativa L.). Untargeted screening of SA metabolites revealed that GT-catalyzed glycosylation was the primary transformation pathway of SAs in rice. Molecular docking identified that the binding sites of SAs on GT (D0TZD6) were responsible for transferring sugar moiety to synthesize polysaccharides and detoxify SAs. Specifically, amino acids in the GT-binding cavity (e.g., GLY487 and CYS486) formed stable hydrogen bonds with SAs (e.g., the sulfonamide group of SD). Molecular dynamics simulations revealed that SAs induced conformational changes in GT ligand binding domain, which was supported by the significantly decreased GT activity and gene expression level. As evidenced by proteomics and metabolomics, SAs inhibited the transfer and synthesis of sugar but stimulated sugar decomposition in rice leaves, leading to the accumulation of mono- and disaccharides in rice leaves. While the differences in the increased sugar content by SD (24.3%, compared with control), SD1 (11.1%), and SD2 (6.24%) can be attributed to their number of methyl groups (0, 1, 2, respectively), which determined the steric hindrance and hydrogen bonds formation with GT. This study suggested that the disturbances on crop sugar metabolism by homologues contaminants are determined by the interaction between the contaminants and the target enzyme, and are greatly dependent on the steric hindrance effects contributed by their side chains. The results are of importance to identify priority pollutants and ensure crop quality in contaminated fields.

Paper-based analytical device for sensitive colorimetric determination of sulfonamides in pharmaceutical samples

Sulfa drugs are frequently used to treat infections, particularly in antibiotic resistant people. There are several techniques available to determine sulfa drugs, however, they are laborious operation, reagent consumption, expensive, and need specialized types of equipment. Here, a new, very simple and inexpensive paper-based analytical device described for the determination of five sulfa drugs: sulfacetamide, sulfadiazine, sulfamerazine, sulfamethoxazole, and sulfathiazole in pharmaceutical preparations. The method is a one-step reaction, based on the colorimetric reaction between acid-hydrolyzed sulfa drugs and 4-dimethylaminobenzaldehyde. Using a smartphone, the RGB value of color intensity was used as an analytical signal. The paper-based device displayed linear ranges of 0.10–5.00 µg mL−1, linear correlations ranging from 0.9903 to 0.9972, limits of detection 0.0030 to 0.0082 µg mL−1, and RSD of ≤0.258 under optimal conditions. The suggested approach was applied for determining five sulfa drugs in pharmaceutical formulations. This approach is appropriate for pharmaceutical applications since it is inexpensive, simple to utilize, sensitive, and selective.

Adverse Cutaneous Drug Reaction

Drug-induced skin disease or cutaneous adverse drug reaction (CADR) is a term encompassing clinical manifestations of the skin, induced by drugs or their metabolites. The skin is the organ most commonly affected by drug reactions, affecting up to 10% of hospitalized patients and can occur in 1–3% of her polypharmacy patients. Most CADRs are mild or self-resolving conditions. The most frequently reported are macular papular rash, urticaria/angioedema, fixed drug eruption and erythema multiforme. Less common but more severe patterns include, drug reactions with eosinophilia and systemic symptoms, and the Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum. Almost any drug can induce CADR, but antibiotics (especially sulfa drugs), nonsteroidal anti-inflammatory drugs, and antiepileptic drugs are most commonly implicated. Various mechanisms are involved in the pathogenesis of CADR, some of which are still unknown. Which may be immune mediated or non-immune mediated Recognition of a specific CADR depends primarily on the physician's ability to perform a detailed clinical examination, an accurate description of the skin lesion morphology, and corroboration of laboratory and/or skin biopsy findings.

Synthesis, biological and antioxidant activity of new diamides derived from sulfonamide drug and local anesthesia

Synthesis, biological and antioxidant activity of new diamides derived from sulfonamide drug and local anesthesia

Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies

To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1HNMR, 13CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin’s performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes. Communicated by Ramaswamy H. Sarma

Multitarget and suspect screening of antimicrobials in soil and manure by means of QuEChERS — liquid chromatography tandem mass spectrometry

The present work aimed to develop an accurate analytical method for the simultaneous analysis of twenty-four antimicrobials in soil:compost and animal manure samples by means of ultra-high performance liquid chromatography coupled to a triple-quadrupole mass spectrometer (UHPLC-QqQ). For this purpose, the effectiveness of two extraction techniques (i.e. focused ultrasound solid–liquid extraction (FUSLE) and QuEChERS (quick, easy, cheap, effective, rugged and safe)) was evaluated, and the clean-up step using solid-phase extraction (SPE) was also thoroughly studied. The method was successfully validated at 10 μg·kg−1, 25 μg·kg−1, and 50 μg·kg−1 showing adequate trueness (70–130%) and repeatability (RSD < 30%), with few exceptions. Procedural limits of quantification (LOQPRO) were determined for soil:compost (0.45 to 7.50 μg·kg−1) and manure (0.31 to 5.53 μg·kg−1) samples. Pefloxacin could not be validated at the lowest level since LOQPRO ≥ 10 μg·kg−1. Sulfamethazine (7.9 ± 0.8 µg·kg−1), danofloxacin (27.1 ± 1.4 µg·kg−1) and trimethoprim (4.9 ± 0.5 µg·kg−1) were detected in soil samples; and tetracycline (56.8 ± 2.8 µg·kg−1), among other antimicrobials, in the plants grown on the surface of the studied soil samples. Similarly, sulfonamides (SAs), tetracyclines (TCs) and fluoroquinolones (FQs) were detected in sheep manure in a range of 1.7 ± 0.3 to 93.3 ± 6.8 µg·kg−1. Soil and manure samples were also analysed through UHPLC coupled to a high-resolution mass-spectrometer (UHPLC-qOrbitrap) in order to extend the multitarget method to suspect screening of more than 22,281 suspects. A specific transformation product (TP) of sulfamethazine (formyl-sulfamethazine) was annotated at 2a level in manure samples, among others. This work contributes to the efforts that have been made in the last decade to develop analytical methods that allow multitarget analysis of a wide variety of antimicrobials, including TPs, which is a complex task due to the diverse physicochemical properties of the antimicrobials.

Comparison of antibiotic-resistant Escherichia coli and extra-intestinal pathogenic E. coli from main river basins under different levels of the sewer system development

Antimicrobial-resistant Escherichia coli in the aquatic environments is considered a strong indicator of sewage or animal waste contamination and antibiotic pollution. Sewer construction and wastewater treatment plant (WWTP) infrastructure may serve as concentrated point sources of contamination of antibiotic-resistant bacteria and antibiotic resistance genes. In this study, we focused on the distribution of antimicrobial-resistant E. coli in two rivers with large drainage areas and different urbanisation levels. E. coli from Kaoping River with drainage mainly from livestock farming had higher resistance to antibiotics (e.g. penicillins, tetracyclines, phenicols, aminoglycosides, and sulpha drugs) and presented more positive detection of antibiotic-resistance genes (e.g. ampC, blaTEM, tetA, and cmlA1) than that from Tamsui River. In Kaoping River with a lower percentage of sewer construction nearby (0–30%) in contrast to a higher percentage of sewer construction (55–92%) in Tamsui River, antimicrobial-resistant E. coli distribution was related to livestock farming waste. In Tamsui River, antimicrobial resistant E. coli isolates were found more frequently in the downstream drainage area of WWTPs with secondary water treatment than that of WWTPs with tertiary water treatment. The Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR showed that the fingerprinting group was significantly related to the sampling site (p < 0.01) and sampling date (p < 0.05). By utilising ERIC-PCR in conjunction with antibiotic susceptibility and antibiotic-resistance gene detection, the relationship among different strains of E. coli could be elucidated. Furthermore, we identified the presence of six extra-intestinal pathogenic E. coli isolates and antibiotic-resistant E. coli isolates near drinking water sources, posing a potential risk to public health through community transmission. In conclusion, this study identified environmental factors related to antibiotic-resistant bacteria and antibiotic-resistance gene contamination in rivers during urban development. The results facilitate the understanding of specific management of different waste streams across different urban areas. Periodic surveillance of the effects of WWTPs and livestock waste containing antibiotic-resistant bacteria and antibiotic-resistance genes on river contamination is necessary.

Assisted wet deposition targeted synthesis of Co-N coordination single-atom catalysts for efficient Fenton-like catalytic degradation of micropollutants

Assisted wet deposition methods to localize the active phase metal on the carrier surface and prevent atomic aggregation during conventional heat treatment are strongly preferred. Herein, single-atom cobalt catalysts (SA-Co-PCN) with different metal-central content were target-prepared using a combination of impregnation and secondary annealing on polymerized carbon nitride (PCN) through reticular confinement. Fitting the coordination configuration of the Co-N pathway within the first coordination shell according to quantitative EXAFS indicated that the ligancy of Co-N was 4. The removal efficiency of representative micropollutants in the SA-Co-PCN/PMS system achieved 100% within 15 min. The outstanding degradation properties of micropollutants were ascribed to the SA-Co-PCN boosts PMS to a 1O2-dominated system. Moreover, the effects of substituents on the degradation behavior and ecotoxicology of sulfonamides (SAs) in PMS-activated systems were investigated in depth. The combination of DFT theoretical calculations and LC-MS further confirmed that the similar electron-rich sites on the SAs molecules allowed for commonality in the degradation pathway. Both S-N bond and C-S bond fragments became the initial attack and cleavage sites in the series of SAs. Ecotoxicity predictions indicated that most intermediates of SAs exhibited lower acute and chronic toxicity, especially acute toxicity, than the parent compounds. Environmental ImplicationAssisted wet deposition to localize the active phase metal on the carrier surface allows easy target formation of single-atom cobalt catalysts (SA-Co-PCN), which could boost PMS to a 1O2-dominated system for efficient oxidation of typical micropollutants. The degradation behavior and ecotoxicology of sulfonamides in the SA-Co-PCN/PMS system were investigated in depth, revealing that most intermediates of sulfonamides exhibited lower acute and chronic toxicity, especially acute toxicity, than the parent compounds. This work provides a strategy for the development of facilely prepared single-atom catalysts and contributes to the development and application potential of PMS advanced oxidation technology for water pollution control.

Antibacterial Azo Dyes Containing Sulfa Drug Moieties and Their Colour Assessment on Printing Polyester Fabric

AbstractSynthesis of a new series of biologically active dyes containing the sulfa drug nucleus and its use in polyester silk screen printing were presented. Synthesis was performed via azo coupling with C and N Nucleophiles. Spectroscopic tools were used to characterize the synthesized azo derivatives. Also, testing of their printing properties, including fastness to washing, light, rubbing, perspiration, and sublimation were evaluated. The new dyes showed respectable fastness and good antibacterial resistance to the growth of certain species of gram‐positive and gram‐negative bacteria. These low‐cost facile synthesized biologically active dyes could be used for sterilizing textiles.

Photoelectrocatalytic Oxidation of Sulfamethazine on TiO2 Electrodes

The photoelectrocatalytic degradation and mineralization of sulfamethazine (SMT), a sulfonamide drug, were explored in aqueous solution. Working electrodes with TiO2 coatings on Ti substrates (TiO2/Ti) were used, which were produced by the dip coating method. TiO2 film electrodes were analyzed by scanning electron microscopy (SEM) and X-ray diffraction (XRD) following annealing at 500 °C for 1.5 h. To photoelectrochemically characterize them, photocurrents vs. applied potential curves were used. The photoelectrocatalytic efficiency (PEC) of the TiO2/Ti electrodes regarding the oxidation of SMT has been assessed with reference to degradation and mineralization under different experimental conditions. The selected drug molecule was effectively degraded following the Langmuir–Hinshelwood (L-H) kinetic model. The degradation efficiency was shown to increase with increasing applied potential bias up to +1.5 V vs. Ag/AgCl. It was found to be more favorable in acidic environments compared to alkaline ones. A decrease in the destruction rate constant was recorded when the pH was increased from 3 to 5.6 (natural pH) and 9. The decomposition rate was shown to first increase and subsequently reach a saturation value at high concentrations of SMT, indicating that the degradation also depends on other parameters (e.g., the rate of the charge or the mass transfer on the electrode double layer). The results of the photoelectrocatalytic experiments were compared to those of electrochemical (EC) and photocatalytic (PC) degradation of SMT. A significant enhancement was recorded in the case of the PEC degradation, leading at +1.5 V to an increase of the apparent rate constants of degradation, k, and mineralization, kTOC, of 153 and 298%, respectively, compared to the simple photocatalytic process.

Behavioral and ecotoxicology of sulfonamide metabolites in the aquatic environment.

Sulfonamides (SAs) are the first broad-spectrum synthetic antimicrobial agents used in human health and veterinary medicine. The majority of SAs entering human body is discharged into aquatic environment in the form of parent material or metabolites. The residues of SAs and their metabolites in the aquatic environment and the development of drug resistance can be serious threats to ecosystems and human health. We summarized recent advances in the research of SAs. The main metabolite types of SAs and the distribution characteristics of metabolites in different aquatic environments were introduced. The ecotoxicology of SAs metabolites, especially the distribution and hazards of sulfonamide resistance genes (sul-ARGs), were discussed with emphasis. Finally, the future research works were proposed. This paper could provide basic information for further research on SAs.

Characterization, optimization, and physicochemical characteristics of polyvinyl alcohol containing sulfa drug

Characterization, optimization, and physicochemical characteristics of polyvinyl alcohol containing sulfa drug

Sulfonamides and β-lactam antibiotic residues and human health risk assessment in commercial chicken meat sold in Nairobi City, Kenya

The use of antibiotic pharmaceuticals in chicken husbandry has risen steadily over time. Antibiotic residues in chicken meat poses risks to human health in addition to their contribution to the advancement of antibiotic resistance. Despite the increased use of antibiotics in chicken farming in Kenya, assessments of the residues and human exposure have not been conducted. In this study, the sulfonamides (SAs); sulfapyridine (SPD), sulfadiazine (SDZ) and sulfamethazine (SMZ) and the β-lactams (βLs); ampicillin (AMP), penicillin G (PEG) and amoxicillin (AMX) were determined in three chicken meat types; ex-layers, broilers, and indigenous meat marketed in Nairobi City, Kenya. Residual SAs ranged from 0.1 to 154.4 μg kg−1, with SPD recording the highest concentration in ex-layers’ chicken meat samples. A range of 19.7 to 309.0 μg kg−1of BLs was found, where the highest amount represented AMX in ex-layers. Mean AMX contents in all chicken types, and AMP in broilers were above the Maximum Residue Limits (MRLs). For SAs, only SPD mean content was above MRL in ex-layers. Human health risks from exposure to antibiotic-contaminated chicken meat was evaluated using % ADI. All tested βLs were of no risk (<1% ADI) to human health. SPD and SDZ posed considerable risk (1–5% ADI) in some chicken meat, whereas SPD in ex-layers’ chicken meat posed distinctive risk (>5% ADI) to children. Considering the co-occurrence of different types of antibiotics in same samples, obtained MRLs and % ADI (for some of the antibiotics) are indicative of potential human health risks. Information is valuable in provoking response from concerned agencies and fostering activities that advocate for judicious use of antibiotics.

Distribution, removal and ecological risk assessment of antibiotics in leachate from municipal solid waste incineration plants in Shanghai, China

Leachate from Municipal Solid Waste (MSW) incineration plants contains multiple antibiotics. However, current knowledge of antibiotics in such leachate is very limited compared to landfill leachate. In this study, the distribution, removal and ecological risks of 8 sulfonamides (SAs), 4 quinolones (FQs), and 4 macrolides (MLs) antibiotics in leachate from three MSW incineration plants in Shanghai were investigated. The results showed that 12 types of target antibiotics were detected at high concentrations (7737.3–13,758.7 ng/L) in the fresh leachate, exceeding the concentrations reported for landfill leachate. FQs were the dominant antibiotics detected in all three fresh leachates, accounting for >60 % of the total detected concentrations. The typical “anaerobic-anoxic/aerobic-anoxic/aerobic-ultrafiltration” treatment process removed the target antibiotics effectively (89.0 %–93.4 %), of which the anaerobic unit and the primary anoxic/aerobic unit were the most important antibiotic removal units. Biodegradation was considered to be the dominant removal mechanism, removing 78.11 %–92.37 % of antibiotics, whereas sludge adsorption only removed 1.02 %–10.89 %. Antibiotic removal was significantly correlated with leachate COD, pH, TN, and NH3-N, indicating that they may be influential factors for antibiotic removal. Ecological risk assessment revealed that ofloxacin (OFX) and enrofloxacin (EFX) in the treated leachate still posed high risks to algae and crustaceans. This research provides insights into the fate of antibiotics in leachate.

“Data fusion” quantitative read-across structure-activity-activity relationships (q-RASAARs) for the prediction of toxicities of binary and ternary antibiotic mixtures toward three bacterial species

Antibiotics are often found in the environment as pollutants. They are usually found as mixtures in the environment and may produce toxicity against different ecological species due to joint exposure in the sub-optimal range. Sometimes the degradation products of parent chemicals also interact with it and cause mixture toxicity. In this study, we have developed three different mixture-Quantitative Structure-Activity Relationship (mixture-QSAR) models for three different bacterial species (Vibrio fischeri, Escherichia coli, and Bacillus subtilis). The toxicity data were collected from a previous experimental report in the literature, which comprised binary and ternary mixtures of sulfonamides (SAs), sulfonamide potentiators (SAPs), and tetracyclines (TCs). We have also explored the interspecies modeling to find inter-correlation among the toxicity of these studied organisms and have developed quantitative structure activity-activity relationship (QSAAR) models by employing the “data fusion” quantitative read-across structure-activity–activity relationship (q-RASAAR) and partial least squares (PLS) regression algorithms. All the models are strictly validated using both internal and external validation tests as suggested in the OECD guidelines. Three different mixing rules have been used in this study for descriptor computations to incorporate the additive and interaction effects among the mixture components. To the best of our knowledge, this is the first report of interspecies mixture toxicity models which can predict the cellular toxicity of binary and ternary mixtures against any of the three above-mentioned organisms.