[Characteristics of Microorganisms and Antibiotic Resistance Genes of the Riparian Soil in the Lanzhou Section of the Yellow River].

Riparian soil is a critical area of watersheds. The characteristics of biological contaminants in riparian soil affect the pollution control of the watershed water environment. Thus, the microbial community structure, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) in the riparian soil of the Lanzhou section of the Yellow River were investigated by analyzing the characteristics of soil samples collected from farmland, mountains, and industrial land. The results showed that the Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant phyla in the riparian soil of Lanzhou section of the Yellow River. The microbial structure in the riparian soil was significantly correlated with the land use type (P < 0.05). The α diversity index of bacterial communities in land types was in the order of farmland > mountain > industry. Sulfonamide-typed ARGs were the most dominant genes in the soil of the Lanzhou section of the Yellow River Basin, among which the sul1 gene had the highest abundance, 20-36 000 times that of other detected ARGs. Moreover, the total absolute abundance of ARGs in industrial soil was the highest. Principal coordinate analysis (PCoA) displayed that the ARGs characteristics had a significant correlation with land types (P < 0.05), and intl1 and tnpA-04 drove the diffuseness of sulfonamide and tetracycline ARGs, respectively. Redundancy analysis (RDA) demonstrated that the content of inorganic salt ions and total phosphorus in the soil of the riparian zone of the Yellow River Lanzhou section were the main environmental factors, modifying the distribution of the microbial structure. Halobacterota and Acidobacteriota were the main microflora that drove the structural change in ARGs.

A review on carbon-based biowaste and organic polymer materials for sustainable treatment of sulfonamides from pharmaceutical wastewater.

Frequent detection of sulfonamides (SAs) pharmaceuticals in wastewater has necessitated the discovery of suitable technology for their sustainable remediation. Adsorption has been widely investigated due to its effectiveness, simplicity, and availability of various adsorbent materials from natural and artificial sources. This review highlighted the potentials of carbon-based adsorbents derived from agricultural wastes such as lignocellulose, biochar, activated carbon, carbon nanotubes graphene materials as well as organic polymers such as chitosan, molecularly imprinted polymers, metal, and covalent frameworks for SAs removal from wastewater. The promising features of these materials including higher porosity, rich carbon-content, robustness, good stability as well as ease of modification have been emphasized. Thus, the materials have demonstrated excellent performance towards the SAs removal, attributed to their porous nature that provided sufficient active sites for the adsorption of SAs molecules. The modification of physico-chemical features of the materials have been discussed as efficient means for enhancing their adsorption and reusable performance. The article also proposed various interactive mechanisms for the SAs adsorption. Lastly, the prospects and challenges have been highlighted to expand the knowledge gap on the application of the materials for the sustainable removal of the SAs.

Synthesis, molecular docking analysis, drug-likeness evaluation, and inhibition potency of new pyrazole-3,4-dicarboxamides incorporating sulfonamide moiety as carbonic anhydrase inhibitors.

A series of novel pyrazole-dicarboxamides were synthesized from pyrazole-3,4-dicarboxylic acid chloride and various primary and secondary sulfonamides. The structures of the new compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.024-0.496 µM for hCA I and 0.006-5.441 µM for hCA II. Compounds 7a and 7i showed nanomolar level of inhibition of hCA II, and these compounds exhibited high selectivity for this isoenzyme. Molecular docking studies were performed between the most active compounds 7a, 7b, 7i, and the reference inhibitor AAZ and the hCAI and hCAII to investigate the binding mechanisms between the compounds and the isozymes. These compounds showed better interactions than the AAZ. ADMET and drug-likeness analyses for the compounds have shown that the compounds can be used pharmacologically in living organisms.

Selective Bacterial Growth Inactivation by pH-Sensitive Sulfanilamide Functionalized Carbon Dots.

Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth inactivation. Sulfanilamide is a prodrug; aromatic hetero cyclization of the amine moiety along with other chemical modifications produces an active pharmacological compound (chloromycetin and miconazole), mostly administered for the treatment of various microbial infections. On the other hand, the efficacy of the sulfanilamide molecule as a drug for antimicrobial activity was very low. We anticipated that the binding of the sulfanilamide molecule on the carbon dot (CD) surface may form antibacterial CDs. Citric acid was hybridized with sulfanilamide during the hydrothermal preparation of the CDs. The molecular fragments of bioactivated sulfanilamide molecule play a crucial role in bacterial growth inactivation for Gram-positive and Gram-negative bacteria. The functional groups of citric acid and sulfanilamide were conserved during the CD formation, facilitating the zwitterionic behavior of CDs associated with its photophysical activity. At low concentrations of CDs, the antibacterial activity was apparent for Gram-positive bacteria only. This Gram-positive bacteria selectivity was also rationalized by zeta potential measurement.

Natural attenuation of sulfonamides and metabolites in contaminated groundwater - Review, advantages and challenges of current documentation techniques.

Sulfonamides are applied worldwide as antibiotics. They are emerging contaminants of concern, as their presence in the environment may lead to the spread of antibiotic resistance genes. Sulfonamides are present in groundwater systems, which suggest their persistence under certain conditions, highlighting the importance of understanding natural attenuation processes in groundwater. Biodegradation is an essential process, as degradation of sulfonamides reduces the risk of antibiotic resistance spreading. In this review, natural attenuation, and in particular assessment of biodegradation, is evaluated for sulfonamides in groundwater systems. The current knowledge level on biodegradation is reviewed, and a scientific foundation is built based on sulfonamide degradation processes, pathways, metabolites and toxicity. An overview of bacterial species and related metabolites is provided. The main research effort has focused on aerobic conditions while investigations under anaerobic conditions are lacking. The level of implementation in research is laboratory scale; here we strived to bridge towards field application and assessment, by assessing approaches commonly used in monitored natural attenuation. Methods to document contaminant mass loss are assessed to be applicable for sulfonamides, while the approach is limited by a lack of reference standards for metabolites. Furthermore, additional information is required on relevant metabolites in order to improve risk assessments. Based on the current knowledge on biodegradation, it is suggested to use the presence of substituent-containing metabolites from breakage of the sulfonamide bridge as specific indicators of degradation. Microbial approaches are currently available for assessment of microbial community's capacities, however, more knowledge is required on indigenous bacteria capable of degrading sulfonamides and on the impact of environmental conditions on biodegradation. Compound specific stable isotope analysis shows great potential as an additional in situ method, but further developments are required to analyse for sulfonamides at environmentally relevant levels. Finally, in a monitored natural attenuation scheme it is assessed that approaches are available that can uncover some processes related to the fate of sulfonamides in groundwater systems. Nevertheless, there are still unknowns related to relevant bacteria and metabolites for risk assessment as well as the effect of environmental settings such as redox conditions. Alongside, uncovering the fate of sulfonamides in future research, the applicability of the natural attenuation documentation approaches will advance, and provide a step towards in situ remedial concepts for the frequently detected sulfonamides.

Isolation, identification and whole-genome analysis of an Achromobacter strain with a novel sulfamethazine resistance gene and sulfamethazine degradation gene cluster.

A sulfamethazine (SM2) degrading strain, Achromobacter mucicolens JD417, was isolated from sulfonamide-contaminated sludge using gradient acclimation. Optimal SM2 degradation conditions were pH 7, 36 °C, and 5 % inoculum, achieving a theoretical maximum degradation rate of 48 % at 50 ppm SM2. Cell growth followed the Haldane equation across different SM2 concentrations. Whole-genome sequencing of the strain revealed novel functional annotations, including a sulfonamide resistance gene (sul4) encoding dihydropteroate synthase, two flavin-dependent monooxygenase genes (sadA and sadB) crucial for SM2 degradation, and unique genomic islands related to metabolism, pathogenicity, and resistance. Comparative genomics analysis showed good collinearity and homology with other Achromobacter species exhibiting organics resistance or degradation capabilities. This study reveals the novel molecular resistance and degradation mechanisms and genetic evolution of an SM2-degrading strain, providing insights into the bioremediation of sulfonamide-contaminated environments.

A novel premixing strategy for highly sensitive detection of nitrite on paper-based analytical devices.

BACKGROUND: Nitrite has been involved in many food processing techniques and its excessive consumption is closely related to the development of different diseases. Therefore, highly sensitive detection of nitrite is significant to ensure food safety. RESULT: This study presents a simple and novel strategy for the highly sensitive detection of nitrite in food using paper-based analytical devices (PADs). In this proposed strategy, the nitrite present in the sample undergoes efficient diazotization when initially mixed with sulfanilamide solution before reacting with N-(1-naphthyl) ethylenediamine dihydrochloride (NED) coated on the detection region of the PAD, leading to the maximum production of colored azo compounds. Specifically, within the concentration range of 0.1-20 mg/L, the LOD and LOQ for the nitrite assay using the premixing strategy are determined as 0.053 mg/L and 0.18 mg/L, respectively which significantly surpass the corresponding values of 0.18 mg/L (LOD) and 0.61 mg/L (LOQ) achieved with the regular Griess reagent analysis. SIGNIFICANCE: The study highlights the critical importance of the premixing strategy in nitrite detection. Under optimized conditions, the strategy demonstrates an excellent limit of detection (LOD) and limit of quantification (LOQ) for nitrite detection in eight different meat samples. In addition to its high precision, the strategy is applicable in the field of nitrite analysis. This strategy could facilitate rapid and cost-effective nitrite analysis in real food samples, ensuring food safety and quality analysis.

Cooperation among nitrifying microorganisms promotes the irreversible biotransformation of sulfamonomethoxine.

Ammonia-oxidizing microorganisms, including AOA (ammonia-oxidizing archaea), AOB (ammonia-oxidizing bacteria), and Comammox (complete ammonia oxidization) Nitrospira, have been reported to possess the capability for the biotransformation of sulfonamide antibiotics. However, given that nitrifying microorganisms coexist and operate as communities in the nitrification process, it is surprising that there is a scarcity of studies investigating how their interactions would affect the biotransformation of sulfonamide antibiotics. This study aims to investigate the sulfamonomethoxine (SMM) removal efficiency and mechanisms among pure cultures of phylogenetically distinct nitrifiers and their combinations. Our findings revealed that AOA demonstrated the highest SMM removal efficiency and rate among the pure cultures, followed by Comammox Nitrospira, NOB, and AOB. However, the biotransformation of SMM by AOA N. gargensis is reversible, and the removal efficiency significantly decreased from 63.84 % at 167 h to 26.41 % at 807 h. On the contrary, the co-culture of AOA and NOB demonstrated enhanced and irreversible SMM removal efficiency compared to AOA alone. Furthermore, the presence of NOB altered the SMM biotransformation of AOA by metabolizing TP202 differently, possibly resulting from reduced nitrite accumulation. This study offers novel insights into the potential application of nitrifying communities for the removal of sulfonamide antibiotics (SAs) in engineered ecosystems.

Sacrificial template synthesis of hollow sulfonate group functionalized microporous organic network for efficient solid phase extraction of sulfonamide antibiotics from milk and honey samples.

The highly conjugated and hydrophobic characteristics of microporous organic networks (MONs) have largely impeded their broad applications in sample pretreatment especially for the polar or ionic analytes. In this work, a novel uniform hollow shaped sulfonate group functionalized MON (H-MON-SO3H-2) was synthesized via the sacrificial template method for the efficient solid phase extraction (SPE) of sulfonamides (SAs) from environmental water, milk, and honey samples prior to HPLC analysis. H-MON-SO3H-2 exhibited large specific surface area, penetrable space, good stability, and numerous hydrogen bonding, electrostatic, hydrophobic and π-π interaction sites, allowing sensitive SPE of SAs with wide linear range (0.150-1000 µg L-1), low limit of detection (0.045-0.188 µg L-1), good precisions (intra-day and inter-day RSD < 7.3%, n = 5), large enrichment factors (95.7-98.5), high adsorption capacities (250.4-545.0 mg g-1), and satisfactory reusability (more than 80 times). Moreover, the established method was successfully applied to extract SAs from spiked samples with the recoveries of 86.1-104.3%. This work demonstrated the great potential of H-MON-SO3H-2 in the efficient SPE of trace SAs in complex environmental water and food samples and revealed the prospect of hollow MONs in sample pretreatment.

Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors.

The aberrant activation of NLRP3 inflammasome has been observed in various human diseases. Targeting the NLRP3 protein with small molecule inhibitors shows immense potential as an effective strategy for disease intervention. Herein, a series of novel biphenyl-sulfonamide NLRP3 inflammasome inhibitors were designed and synthesized. The representative compound H28 was identified as potent and specific NLRP3 inflammasome inhibitor with IC50 values of 0.57 µM. Preliminary mechanistic studies have revealed that compound H28 exhibits direct binding to the NLRP3 protein (KD: 1.15 µM), effectively inhibiting the assembly and activation of the NLRP3 inflammasome. The results in a mouse acute peritonitis model revealed that H28 effectively inhibit the NLRP3 inflammasome pathway, demonstrating their anti-inflammatory properties. Our findings strongly support the further development of H28 as potential lead compound for treating NLRP3-related diseases.

2-Thioxo-3,4-dihydropyrimidine and thiourea endowed with sulfonamide moieties as dual EGFRT790M and VEGFR-2 inhibitors: Design, synthesis, docking, and anticancer evaluations.

The effectiveness of a new series of thiopyrimidine and thiourea containing sulfonamides moieties was tested on HCT-116, MCF-7, HepG2, and A549. HepG2 cell line was the one that all the new derivatives affected the most. The greatest potent compounds against the four HepG2, HCT116, MCF-7, and A549 cell lines were 8f and 8g with IC50 = 4.13, 6.64, 5.74, 6.85 µM and 4.09, 4.36, 4.22, 7.25 µM correspondingly. Compound 8g exhibited higher activity than sorafenib against HCT116 and MCF-7 but exhibited lower activity against HepG2 and A549. Moreover, compounds 8f and 8g exhibited higher activities than erlotinib on HepG2, HCT116, and MCF-7 but demonstrated lower activity on A549. The most potent cytotoxic derivatives 6f, 6g, 8c, 8d, 8e, 8f, and 8g were examined on normal VERO cell lines. Our derivatives have low toxicity on VERO cells with IC50 values ranging from 32.05 to 53.15 µM. Additionally, all compounds were assessed for dual VEGFR-2 and EGFRT790M inhibition effects. Compounds 8f and 8g were the most potent derivatives inhibited VEGFR-2 at IC50 value of 0.88 and 0.90 µM, correspondingly. As well, derivatives 8f and 8g could inhibit EGFRT790M demonstrating strongest effects with IC50 = 0.32 and 0.33 µM sequentially. Additionally, the greatest active derivatives ADMET profile was evaluated in relationship with sorafenib and erlotinib as reference agents. The data attained from docking were greatly related to that achieved from the biological testing.

Strain-level diversity in sulfonamide biodegradation: adaptation of Paenarthrobacter to sulfonamides.

The widespread occurrence of sulfonamides raises significant concerns about the evolution and spread of antibiotic resistance genes. Biodegradation represents not only a resistance mechanism but also a clean-up strategy. Meanwhile, dynamic and diverse environments could influence the cellular function of individual sulfonamide-degrading strains. Here, we present Paenarthrobacter from different origins that demonstrated diverse growth patterns and sulfonamide-degrading abilities. Generally, the degradation performance was largely associated with the number of sadA gene copies and also relied on its genotype. Based on the survey of sad genes in the public database, an independent mobilization of transposon-borne genes between chromosome and plasmid was observed. Insertions of multiple sadA genes could greatly enhance sulfonamide-degrading performance. Moreover, the sad gene cluster and sadA transposable element showed phylogenetic conservation currently, being identified only in two genera of Paenarthrobacter (Micrococcaceae) and Microbacterium (Microbacteriaceae). Meanwhile, Paenarthrobacter exhibited a high capacity for genome editing to adapt to the specific environmental niche, opening up new opportunities for bioremediation applications.

Detection of antibiotic residues in groundwater with a validated multiresidue UHPLC-MS/MS quantification method.

The occurrence of antibiotic residues in the environment has received considerable attention because of their potential to select for bacterial resistance. The overuse of antibiotics in human medicine and animal production results in antibiotic residues entering the aquatic environment, but concentrations are currently not well determined. This study investigates the occurrence of antibiotics in groundwater in areas strongly related to agriculture and the antibiotic treatment of animals. A multiresidue method was validated according to EU Regulation 2021/808, to allow (semi-)quantitative analysis of 78 antibiotics from 10 different classes: ß-lactams, sulfonamides, tetracyclines, lincosamides, amphenicols, (fluoro)quinolones, macrolides, pleuromutilins, ansamycins and diaminopyrimidines using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). This method was used to test different storage conditions of these water samples during a stability study over a period of 2 weeks. Sulfonamides, lincosamides and pleuromutilins were the most stable. Degradation was most pronounced for ß-lactam antibiotics, macrolides and ansamycins. To maintain stability, storage of samples at -18 °C is preferred. With the validated method, antibiotic residues were detected in groundwater, sampled from regions associated with intensive livestock farming in Flanders (Belgium). Out of 50 samples, 14% contained at least one residue. Concentrations were low, ranging from < LOD to 0.03 µg/L. Chloramphenicol, oxolinic acid, tetracycline and sulfonamides (sulfadiazine, sulfadoxine, sulfamethazine and sulfisoxazole) were detected. This study presents a new method for the quantification of antibiotic residues, which was applied to investigate the presence of antibiotic residues in groundwater in Flanders.

Comparing the photodegradation of typical antibiotics in ice and in water: Degradation kinetics, mechanisms, and effects of dissolved substances.

New antibiotic contaminants have been detected in both surface waters and natural ice across cold regions. However, few studies have revealed distinctions between their ice and aqueous photochemistry. In this study, the photodegradation and effects of the main dissolved substances on the photolytic kinetics were investigated for sulfonamides (SAs) and fluoroquinolones (FQs) in ice/water under simulated sunlight. The results showed that the photolysis of sulfamethizole (SMT), sulfachloropyridazine (SCP), enrofloxacin (ENR) and difloxacin (DIF) in ice/water followed the pseudo-first-order kinetics with their quantum yields ranging from 4.93 × 10-3 to 11.15 × 10-2. The individual antibiotics experienced disparate photodegradation rates in ice and in water. This divergence was attributed to the concentration-enhancing effect and the solvent cage effect that occurred in the freezing process. Moreover, the main constituents (Cl-, HASS, NO3- and Fe(III)) exhibited varying degrees of promotion or inhibition on the photodegradation of SAs and FQs in the two phases (p < 0.05), and these effects were dependent on the individual antibiotics and the matrix. Extrapolation of the laboratory data to the field conditions provided a reasonable estimate of environmental photolytic half-lives (t1/2,E) during midsummer and midwinter in cold regions. The estimated t1/2,E values ranged from 0.02 h for ENR to 14 h for SCP, which depended on the reaction phases, latitudes and seasons. These results revealed the similarities and differences between the ice and aqueous photochemistry of antibiotics, which is important for the accurate assessment of the fate and risk of these new pollutants in cold environments.

Insights into the pH-dependent interactions of sulfadiazine antibiotic with soil particle models.

Sulfonamide antibiotics (SAs) are widely used as a broad-spectrum antibiotic, leading to global concerns due to their potential soil accumulation and subsequent effects on ecosystems. SAs often exhibit remarkable environmental persistence, necessitating further investigation to uncover the ultimate destiny of these molecules. In this work, molecular dynamics simulations combined with complementary quantum chemistry calculations were employed to investigate the influence of pH on the behavior of sulfadiazine (SDZ, a typical SAs) in soil particle models (silica, one of the main components of soil). Meanwhile, the quantification of SDZ molecules aggregation potential onto silica was further extended. SDZ molecules tend to form a monolayer on the soil surface under acidic conditions while forming aggregated adsorption on the surface under neutral conditions. Due to the hydrophilicity of the silica, multiple hydration layers would form on its surface, hindering the further adsorption of SDZ molecules on its surface. The calculated soil-water partition coefficient (Psoil/water) of SDZ+ and SDZ were 9.01 and 7.02, respectively. The adsorption evaluation and mechanisms are useful in controlling the migration and transformation of SAs in the soil environment. These findings provide valuable insights into the interactions between SDZ and soil components, shedding light on its fate and transport in the environment.

Transformation process and phytotoxicity of sulfamethoxazole and N4-acetyl-sulfamethoxazole in rice.

Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20.36 ± 1.98 µg/g (roots) and 5.62 ± 1.17 µg/g (shoots), and with SMX concentrations up to 15.97 ± 2.53 µg/g (roots) and 3.22 ± 0.789 µg/g (shoots). A total of 18 intermediate transformation products of SMX were identified by nontarget screening using Orbitrap-HRMS, revealing pathways such as deamination, hydroxylation, acetylation, formylation, and glycosylation. Notably, NASMX transformed back into SMX in rice, a novel finding. Transcriptomic analysis highlights the involvements of cytochrome P450 (CYP450), acetyltransferase (ACEs) and glycosyltransferases (GTs) in these biotransformation pathways. Moreover, exposure to SMX and NASMX disrupts TCA cycle, amino acid, linoleic acid, nucleotide metabolism, and phenylpropanoid biosynthesis pathways of rice, with NASMX exerting a stronger impact on metabolic networks. These findings elucidate the sulfonamides' metabolism, phytotoxicity mechanisms, and contribute to assessing food safety and human exposure risk amid antibiotic pollution.

When I use a word . . . Medicines regulation-diethylene glycol.

In 1937, when diethylene glycol was used as a solvent in the preparation of a medicinal product, an elixir of sulfanilamide, resulting in deaths, public outcry hastened the promulgation of an act that had been in preparation in the USA for several years, but which had met with opposition from pharmaceutical companies. The 1938 Food, Drug, and Cosmetics Act, as it was known, gave greater powers to the then recently formed Food and Drug Administration (FDA) in regulating the contents of medicinal formulations. Nevertheless, although similar regulatory systems have since been established around the world, episodes of poisoning with diethylene glycol in pharmaceutical formulations, whether deliberately included adulteration or as a contaminant, continue to be reported, generally in developing countries, usually affecting children, and often causing deaths.

How data on transformation products can support the redesign of sulfonamides towards better biodegradability in the environment.

Sulfonamide antibiotics (SUAs) released into the environment can affect environmental und human health, e.g., by accelerating the development and selection of antimicrobial resistant bacteria. Benign by Design (BbD) of SUAs is an effective risk prevention approach. BbD principles aim for fast and complete mineralization or at least deactivation of the SUA after release into the aquatic environment. Main objective was to test if mixtures of transformation products (TPs) generated via photolysis of SUAs can be used as an efficient way to screen for similarly effective but better biodegradable SUA alternatives. Six SUAs were photolyzed (Hg ultraviolet (UV) light), and generated UV-mixtures analysed by high performance liquid chromatography coupled to an UV and tandem mass spectrometry detector. UV-mixtures were screened for antibiotic activity (luminescence bacteria test, LBT, on luminescence and growth inhibition of Aliivibrio Fischeri) and environmental biodegradability (manometric respirometry test, MRT, OECD 301F) using untreated parent SUAs in comparison. Additionally, ready environmental biodegradability of three commercially available hydroxylated sulfanilamide derivatives was investigated. SUA-TPs contributed to acute and chronic bacterial luminescence inhibition by UV-mixtures. LBT's third endpoint, growth inhibition, was not significant for UV-mixtures. However, it cannot be excluded for tested TPs as concentrations were lower than parents' concentrations and inhibition by most parental concentrations tested was also not significant. HPLC analysis of MRT samples revealed that one third of SUA-TPs was reduced during incubation. Three of these TPs, likely OH-SIX, OH-SMX and OH-STZ, were of interest for BbD because the sulfonamide moiety is still present. However, hydroxylated sulfanilamide derivatives, tested to investigate the effect of hydroxylation on biodegradability, were not readily biodegraded. Thus, improving mineralization through hydroxylation as a general rule couldn't be confirmed, and no BbD candidate could be identified. This study fills data gaps on bioactivity and environmental biodegradability of SUAs' TP-mixtures. Findings may support new redesign approaches.

Discovery of non-sulfonamide carbonic anhydrase IX inhibitors through structure-based virtual screening.

Carbonic anhydrase IX (CA IX) is a subtype of the human carbonic anhydrase (hCA) family and exhibits high expression in various solid tumors, rendering it a promising target for tumor therapy. Currently, marketed carbonic anhydrase inhibitors (CAIs) are primarily composed of sulfonamides derivatives, which may have impeded their potential for further expansion. Therefore, we have developed a structure-based virtual screening approach to explore novel CAIs exhibiting distinctive structures and anti-tumor potential in the FDA database. In vitro experiments demonstrated that 3-pyridinemethanol (0.42 µM), procodazole (8.35 µM) and pamidronic acid (8.51 µM) exhibited inhibitory effects on CA IX activity. The binding stability and interaction mode between the CA IX and the hit compounds are further investigated through molecular dynamics simulations and binding free energy calculations. Furthermore, the ADME/Tox prediction results indicated that these compounds exhibited favorable pharmacological properties and minimal toxic side effects. Our study successfully applied computational strategies to discover three non-sulfonamide inhibitors of carbonic anhydrase IX (CA IX) that demonstrate inhibitory activity in vitro. These findings have significant implications for the development of CA IX inhibitors and anti-tumor drugs, contributing to their progress in the field.

Photocatalytic degradation of sulfonamides in suspensions of coral-like graphene carbon nitride with nitrogen vacancies.

Sulfonamides (SNs) belong to a category of broad-spectrum antibiotics, which have attracted growing concerns owing to the adverse effects on ecosystem. In this paper, coral-like graphitic carbon nitrides with nitrogen vacancies were prepared by polymerization of melamine in the presence of NH4Cl, and the effect of NH4Cl amount on the structure and photocatalytic performance of g-C3N4 in degradation of sulfonamide antibiotics such as sulfamethoxazole (SMX), sulfadiazine (SDZ) and sulfathiazole (STZ) was systematically studied. It was found that the addition of NH4Cl results in the formation of coral-like g-C3N4 with nitrogen vacancies, and optimal photocatalyst (PCN-1 sample) prepared with a melamine to NH4Cl mass ratio of 1:1 showed the highest photocatalytic activity towards SNs degradation due to the quick electron-hole migration, efficient separation capacity and excellent photoelectric properties. The electron paramagnetic resonance (EPR) technique was used to determine the reactive oxygen species (ROSs) that are responsible for the degradation of SNs, and the detailed degradation pathway of STZ was proposed according to the identification of the intermediates by liguid chromatography-high resolution mass spectrometry (LC-HRMS).