A cutting-edge electrochemical sensing platform for the simultaneous determination of the residues of antimicrobial drugs, rifampicin and norfloxacin, in water samples.

BACKGROUND: The widespread use and abuse of antibiotics has resulted in the pollution of water sources with antibiotic residues, posing a threat to human health, the environment, and the economy. Therefore, a highly sensitive and selective method is required for their detection in water samples. Herein, advanced ultrasensitive electrochemical sensor platform was developed by integrating gold-silver alloy nanocoral clusters (Au-Ag-ANCCs) with functionalized multi-walled carbon nanotube-carbon paste electrode (f-MWCNT-CPE) and choline chloride (ChCl) nanocomposites for simultaneously determining the residues of antimicrobial drugs, rifampicin (RAMP) and norfloxacin (NFX), in water samples. RESULTS: The developed sensor (Au-Ag-ANCCs/f-MWCNTs-CPE/ChCl) was extensively characterized using several analytical (UV-Vis, FT-IR, XRD, SEM, and EDX) and electrochemical (EIS, CV, and SWV) techniques. It exhibited outstanding performance in a wide linear range, from 14 pM to 115 µM for RAMP, and from 0.9 nM to 200 µM for NFX, with a limit of detection (LOD, 3σ/m, S/N = 3, n = 5) and a limit of quantification (LOQ, 10σ/m, S/N = 3, n = 5) values of 2.7 pM and 8.85 pM for RAMP, and 0.14 nM and 0.47 nM for NFX, respectively. The sensor also exhibited exceptional reproducibility, stability, and resistance to interference. SIGNIFICANCE: The developed sensor was effectively utilized to determine RAMP and NFX residues in hospital wastewater, river, and tap water samples, yielding recoveries within the range of 96.8-103 % and relative standard deviations below 5 %. Generally, the proposed sensor demonstrated remarkable performance in detecting the target analytes, making it an ideal tool and the first of its kind for addressing global antibiotic residue pollutants in water sources.

Monitoring Photo-Fenton and Photo-Electro-Fenton process of contaminants emerging concern by a gas diffusion electrode using Ca10-xFex-yWy(PO4)6(OH)2 nanoparticles as heterogeneous catalyst.

The catalytic performance of modified hydroxyapatite nanoparticles, Ca10-xFex-yWy(PO4)6(OH)2, was applied for the degradation of methylene blue (MB), fast green FCF (FG) and norfloxacin (NOR). XPS analysis pointed to the successful partial replacement of Ca by Fe. Under photo-electro-Fenton process, the catalyst Ca4FeII1·92W0·08FeIII4(PO4)6(OH)2 was combined with UVC radiation and electrogenerated H2O2 in a Printex L6 carbon-based gas diffusion electrode. The application of only 10 mA cm-2 resulted in 100% discoloration of MB and FG dyes in 50 min of treatment at pH 2.5, 7.0 and 9.0. The proposed treatment mechanism yielded maximum TOC removal of ∼80% and high mineralization current efficiency of ∼64%. Complete degradation of NOR was obtained in 40 min, and high mineralization of ∼86% was recorded after 240 min of treatment. Responses obtained from LC-ESI-MS/MS are in line with the theoretical Fukui indices and the ECOSAR data. The study enabled us to predict the main degradation route and the acute and chronic toxicity of the by-products formed during the contaminants degradation.

Robust antibacterial activity of rare-earth ions on planktonic and biofilm bacteria.

Bacterial infections pose a serious threat to human health, with emerging antibiotic resistance, necessitating the development of new antibacterial agents. Cu2+and Ag+are widely recognized antibacterial agents with a low propensity for inducing bacterial resistance; however, their considerable cytotoxicity constrains their clinical applications. Rare-earth ions, owing to their unique electronic layer structure, hold promise as promising alternatives. However, their antibacterial efficacy and biocompatibility relative to conventional antibacterial agents remain underexplored, and the variations in activity across different rare-earth ions remain unclear. Here, we systematically evaluate the antibacterial activity of five rare-earth ions (Yb3+, Gd3+, Sm3+, Tb3+, and La3+) againstStaphylococcus aureusandPseudomonas aeruginosa, benchmarked against well-established antibacterial agents (Cu2+, Ag+) and the antibiotic norfloxacin. Cytotoxicity is also assessed via live/dead staining of fibroblasts after 24 h rare-earth ion exposure. Our findings reveal that rare-earth ions require higher concentrations to match the antibacterial effects of traditional agents but offer the advantage of significantly lower cytotoxicity. In particular, Gd3+demonstrates potent bactericidal efficacy against both planktonic and biofilm bacteria, while maintaining the lowest cytotoxicity toward mammalian cells. Moreover, the tested rare-earth ions also exhibited excellent antifungal activity againstCandida albicans. This study provides a critical empirical framework to guide the selection of rare-earth ions for biomedical applications, offering a strategic direction for the development of novel antimicrobial agents.

Quantitative assessment, molecular docking and novel metabolic pathways reveal the interaction mechanisms between norfloxacin biodegradation and environmental implications.

Norfloxacin (NOR) is widely used in medicine and animal husbandry, but its accumulation in the environment poses a substantial threat to ecological and human health. Traditional physical, chemical, and rudimentary biological methods often fall short in mitigating NOR contamination, necessitating innovative biological approaches. This study proposes an engineered bacterial consortium found in marine sediment as a strategy to enhance NOR degradation through inter-strain co-metabolism of diverse substrates. Strategically supplementing the engineered bacterial consortium with exogenous carbon sources and metal ions boosted the activity of key degradation enzymes like laccase, manganese peroxidase, and dehydrogenase. Iron and amino acids demonstrated synergistic effects, resulting in a remarkable 70.8% reduction in NOR levels. The innovative application of molecular docking elucidated enzyme interactions with NOR, uncovering potential biodegradation mechanisms. Quantitative assessment reinforced the efficiency of NOR degradation within the engineered bacterial consortium. Four metabolic routes are herein proposed: acetylation, defluorination, ring scission, and hydroxylation. Notably, this study discloses distinctive, co-operative metabolic pathways for NOR degradation within the specific microbial community. These findings provide new ways of understanding and investigating the bioremediation potential of NOR contaminants, which may lead to the development of more sustainable and effective environmental management strategies.

Exploring the Potential of Biochar Derived from Chinese Herbal Medicine Residue for Efficient Removal of Norfloxacin.

One-step carbonization was explored to prepare biochar using the residue of a traditional Chinese herbal medicine, Atropa belladonna L. (ABL), as the raw material. The resulting biochar, known as ABLB4, was evaluated for its potential as a sustainable material for norfloxacin (NOR) adsorption in water. Subsequently, a comprehensive analysis of adsorption isotherms, kinetics, and thermodynamics was conducted through batch adsorption experiments. The maximum calculated NOR adsorption capacity was 252.0 mg/g at 298 K, and the spontaneous and exothermic adsorption of NOR on ABLB4 could be better suited to a pseudo-first-order kinetic model and Langmuir model. The adsorption process observed is influenced by pore diffusion, π-π interaction, electrostatic interaction, and hydrogen bonding between ABLB4 and NOR molecules. Moreover, the utilization of response surface modeling (RSM) facilitated the optimization of the removal efficiency of NOR, yielding a maximum removal rate of 97.4% at a temperature of 304.8 K, an initial concentration of 67.1 mg/L, and a pH of 7.4. Furthermore, the biochar demonstrated favorable economic advantages, with a payback of 852.5 USD/t. More importantly, even after undergoing five cycles, ABLB4 exhibited a consistently high NOR removal rate, indicating its significant potential for application in NOR adsorption.

Magnetic FNS/MILs nanofibers for highly efficient removal of norfloxacin via adsorption and Fenton-like reaction.

Iron-containing MOFs have attracted extensive interest as promising Fenton-like catalysts. In this work, magnetic Fe3O4 nanofiber (FNS)/MOFs composites with stable structure, included FNS/MIL-88B, FNS/MIL-88A and FNS/MIL-100, were prepared via the in-situ solvothermal method. The surface of the obtained fibers was covered by a dense and continuous MOFs layer, which could effectively solve the agglomeration problem of MOFs powder and improved the catalytic performance. The adsorption and catalytic properties of FNS/MOFs composites were evaluated by removal of norfloxacin. FNS/MIL-88B showed the best performance with a maximum adsorption capacity up to 214.09 mg/g, and could degrade 99% of NRF in 60 min. Meanwhile, FNS/MIL-88B had a saturation magnetization of 20 emu/g, and could be rapidly separated by an applied magnetic field. The self-supported nanofibers allowed the adequate contact between MOFs and pollutants, and promoted the catalytic activity and high stability. We believe that this work provided a new idea for the design and preparation of Fenton-like catalysts especially MOFs composites.

Impact of land use-induced soil heterogeneity on the adsorption of fluoroquinolone antibiotics, tested on organic matter pools.

The effects on the adsorption of fluoroquinolone antibiotics of long-term soil heterogeneity induced by land-use were investigated. Three different land use areas with their two organic matter (OM) pools were tested for the adsorption of three antibiotics widely detected in the environment (ciprofloxacin, norfloxacin, ofloxacin). The soils were separated into two size fractions, > 63 µm fraction and < 63 µm fractions for the fast and slow OM pools, respectively. Any effect of land use on adsorption was only observed in the slow pool in the increasing order: arable land, grassland, and forest. The composition of the soil organic matter (SOM) did influence adsorption in the slow pool, but not in the bulk soilsThis was, because: 1) the ratio of the slow pool was low, as in forest, 2) the ratio of the slow pool was high but its adsorption capacity was low due to its SOM composition, as in arable land and grassland. Soils containing a large slow SOM pool fraction with aliphatic dominance were found to be more likely to adsorb micropollutants. It is our contention that the release of contaminated water, sludge, manure or compost into the environment should only be undertaken after taking this into consideration.

Combined contamination of microplastic and antibiotic alters the composition of microbial community and metabolism in wheat and maize rhizosphere soil.

The widespread application of antibiotics and plastic films in agriculture has led to new characteristics of soil pollution. The impacts of combined contamination of microplastics and antibiotics on plant growth and rhizosphere soil bacterial community and metabolisms are still unclear. We conducted a pot experiment to investigate the effects of polyethylene (0.2%) and norfloxacin/doxycycline (5 mg kg-1), as well as the combination of polyethylene and antibiotics, on the growth, rhizosphere soil bacterial community and metabolisms of wheat and maize seedlings. The results showed that combined contamination caused more serious damage to plant growth than individual contamination, and aggravated root oxidative stress responses. The diversity and structure of soil bacterial community were not markedly altered, but the composition of the bacterial community, soil metabolisms and metabolic pathways were altered. The co-occurrence network analysis indicated that combined contamination may inhibit the growth of wheat and maize seedings by simplifying the interrelationships between soil bacteria and metabolites, and altering the relative abundance of specific bacteria genera (e.g. Kosakonia and Sphingomonas) and soil metabolites (including sugars, organic acids and amino acids). The results help to elucidate the potential mechanisms of phytotoxicity of the combination of microplastic and antibiotics.

Fate and removal of fluoroquinolone antibiotics in mesocosmic wetlands: Impact on wetland performance, resistance genes and microbial communities.

The fate of fluoroquinolone antibiotics norfloxacin and ofloxacin were investigated in mesocosmic wetlands, along with their effects on nutrients removal, antibiotic resistance genes (ARGs) and epiphytic microbial communities on Hydrilla verticillate using bionic plants as control groups. Approximately 99% of norfloxacin and ofloxacin were removed from overlaying water, and H. verticillate inhibited fluoroquinolones accumulation in surface sediments compared to bionic plants. Partial least squares path modeling showed that antibiotics significantly inhibited the nutrient removal capacity (0.55) but had no direct effect on plant physiology. Ofloxacin impaired wetland performance more strongly than norfloxacin and more impacted the primary microbial phyla, whereas substrates played the most decisive role on microbial diversities. High antibiotics concentration shifted the most dominant phyla from Proteobacteria to Bacteroidetes and inhibited the Xenobiotics biodegradation function, contributing to the aggravation in wetland performance. Dechloromonas and Pseudomonas were regarded as the key microorganisms for antibiotics degradation. Co-occurrence network analysis excavated that microorganisms degrade antibiotics mainly through co-metabolism, and more complexity and facilitation/reciprocity between microbes attached to submerged plants compared to bionic plants. Furthermore, environmental factors influenced ARGs mainly by altering the community dynamics of differential bacteria. This study offers new insights into antibiotic removal and regulation of ARGs accumulation in wetlands with submerged macrophyte.

Migration and transformation behaviors of antibiotics in water-sediment system under simulated light and wind waves.

Antibiotics can generally be detected in the water-sediment systems of lakes. However, research on the migration and transformation of antibiotics in water-sediment systems based on the influences of light and wind waves is minimal. To address this research gap, we investigated the specific impacts of light and wind waves on the migration and transformation of three antibiotics, norfloxacin (NOR), trimethoprim (TMP), and sulfamethoxazole (SMX), under simulated light and wind waves disturbance conditions in a water-sediment system from Taihu Lake, China. In the overlying water, NOR was removed the fastest, followed by TMP and SMX. Compared to the no wind waves groups, the disturbance of big wind waves reduced the proportion of antibiotics in the overlying water. The contributions of light and wind waves to TMP and SMX degradation were greater than those of microbial degradation. However, the non-biological and biological contributions of NOR to degradation were almost equal. Wind waves had a significant impact on the microbial community changes in the sediment, especially in Methylophylaceae. These results verified the influence of light and wind waves on the migration and transformation of antibiotics, and provide assistance for the risk of antibiotic occurrence in water and sediments.

Application of machine learning in the study of cobalt-based oxide catalysts for antibiotic degradation: An innovative reverse synthesis strategy.

This study addresses antibiotic pollution in global water bodies by integrating machine learning and optimization algorithms to develop a novel reverse synthesis strategy for inorganic catalysts. We meticulously analyzed data from 96 studies, ensuring quality through preprocessing steps. Employing the AdaBoost model, we achieved 90.57% accuracy in classification and an R²value of 0.93 in regression, showcasing strong predictive power. A key innovation is the Sparrow Search Algorithm (SSA), which optimizes catalyst selection and experimental setup tailored to specific antibiotics. Empirical experiments validated SSA's efficacy, with degradation rates of 94% for Levofloxacin and 97% for Norfloxacin, aligning closely with predictions within a 2% margin of error. This research advances theoretical understanding and offers practical applications in material science and environmental engineering, significantly enhancing catalyst design efficiency and accuracy through the fusion of advanced machine learning techniques and optimization algorithms.

Aggregation-induced-emission red carbon dots for ratiometric sensing of norfloxacin and anti-counterfeiting.

The detection of trace antibiotic residues holds significant importance because it's related to food safety and human health. In this study, we developed a new high-yield red-emitting carbon dots (R-CDs) with aggregation-induced emission properties for ratiometric sensing of norfloxacin. R-CDs were prepared in 30 min using an economical and efficient microwave-assisted method with tartaric acid and o-phenylenediamine as precursors, achieving a high yield of 34.4 %. R-CDs showed concentration-dependent fluorescence and aggregation-induced-emission properties. A ratiometric fluorescent probe for detecting the norfloxacin was developed. In the range of 0-40 µM, the intensity ratio of two emission peaks (I445 nm/I395 nm) towards norfloxacin show good linear relationship with its concentrations and a low detection limit was obtained (36.78 nM). In addition, complex patterns were developed for anti-counterfeiting based on different emission phenomenon at different concentrations. In summary, this study designed a novel ratiometric fluorescent probe for detection of norfloxacin, which greatly shortens the detection time and improves efficiency compared with high-performance liquid chromatography and other methods. The study will promote the application of carbon dots in anti-counterfeiting and other related fields, laying the foundation for the preparation of low-cost photosensitive anti-counterfeiting materials.

Iron-driven self-assembly of dopamine into dumbbell-shaped nanozyme for visual and rapid detection of norfloxacin on a smartphone-assisted platform.

Antibiotics in aquatic environments raise health concerns. Therefore, the rapid, on-site, and accurate detection of antibiotic residues is crucial for protecting the environment and human health. Herein, a dumbbell-shaped iron (Fe3+)-dopamine coordination nanozyme (Fe-DCzyme) was developed via an iron-driven self-assembly strategy. It exhibited excellent peroxidase-like activity, which can be quenched by adding l-cysteine to prevent Fe3+/Fe2+ electron transfer but restored by adding norfloxacin. Given the 'On-Off-On' effect of peroxidase-like activity, Fe-DCzyme was used as a colourimetric sensor for norfloxacin detection, and showed a wide linear range from 0.05 to 6.00 µM (R2 = 0.9950) and LOD of 27.0 nM. A portable smartphone-assisted detection platform using Fe-DCzyme was also designed to convert norfloxacin-induced color changes into RGB values as well as to realise the rapid, on-site and quantitative detection of norfloxacin. A good linear relation (0.10-6.00 µM) and high sensitivity (LOD = 79.3 nM) were achieved for the smartphone-assisted Fe-DCzyme detection platform. Its application was verified using norfloxacin spiking methods with satisfactory recoveries (92.66%-119.65%). Therefore, the portable smartphone-assisted Fe-DCzyme detection platform with low cost and easy operation can be used for the rapid, on-site and visual quantitative detection of antibiotic residues in water samples.

Facet-Dependent Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 Dual S-Scheme Photocatalyst as an Efficient Visible-Light-Driven Peroxymonosulfate Activator for Norfloxacin Degradation.

A lack of eco-friendly, highly active photocatalyst for peroxymonosulfate (PMS) activation and unclear environmental risks are significant challenges. Herein, we developed a double S-scheme Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 photocatalyst to activate PMS and investigated its impact on wheat seed germination. We observed an improvement in charge separation by depositing Fe2O3 on the (010) and (110) surfaces of BiVO4. This enhancement is attributed to the formation of a dual S-scheme charge transfer mechanism at the interfaces of Fe2O3/BiVO4(110) and BiVO4(010)/Fe2O3. By introducing PMS into the system, photogenerated electrons effectively activate PMS, generating reactive oxygen species (ROS) such as hydroxyl radicals (·OH) and sulfate radicals (SO4·-). Among the tested systems, the 20% Fe2O3/BiVO4/Vis/PMS system exhibits the highest catalytic efficiency for norfloxacin (NOR) removal, reaching 95% in 40 min. This is twice the catalytic efficiency of the Fe2O3/BiVO4/PMS system, 1.8 times that of the Fe2O3/BiVO4 system, and 5 times that of the BiVO4 system. Seed germination experiments revealed that Fe2O3/BiVO4 heterojunction was beneficial for wheat seed germination, while PMS had a significant negative effect. This study provides valuable insights into the development of efficient and sustainable photocatalytic systems for the removal of organic pollutants from wastewater.

Norfloxacin adsorption by urban green waste biochar: characterization, kinetics, and mechanisms.

Biochar, as a potential adsorbent, has been widely employed to remove pollutants from sewage. In this study, a lignin-based biochar (CB-800) was prepared by a simple high-temperature pyrolysis using urban green waste (Cinnamomum camphora leaves) as a feedstock to remove norfloxacin (NOR) from water. Batch adsorption test results indicated that CB-800 had a strong removal capacity for NOR at a wide range of pH values. The maximum adsorption achieved in the study was 50.90 ± 0.64 mg/g at 298 K. The pseudo-first and second-order kinetic models and the Dubinin-Radushkevich isotherm fitted the experimental data well, indicating that NOR adsorption by CB-800 was a complex process involving both physi-sorption and chemi-sorption. The physical properties of CB-800 were characterized by SEM and BET. The mesoporous structures were formed hierarchically on the surface of CB-800 (with an average pore size of 2.760 nm), and the spatial structure of NOR molecules was more easily adsorbed by mesoporous structures. Combined with Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis, it was showed that the main NOR adsorption mechanisms by CB-800 included ion exchange, π-electron coordination, hydrogen bonding, and electrostatic adsorption. Meanwhile, the reduction of C = O and pyridine nitrogen, and the presence of C-F2, also indicated the occurrence of substitution, addition, and redox. This study not only determined the reaction mechanism between biochar and NOR, but also provides guidance to waste managers for the removal of NOR from water by biochar. It is envisaged that the results will broaden the utilization of urban green waste.

Efficiency and mechanism of enhanced norfloxacin removal using amorphous TiO2-modified biochar.

Inadequate treatment of antibiotic-contaminated wastewater, including compounds such as norfloxacin (NOR), poses a substantial treat to both ecological safety and human well-being. An innovative approach was devised to address NOR pollution using amorphous TiO2 modified biochar (A-TiO2/BC) prepared via sol-gel impregnation. The resultant had a commendably specific surface area of 131.8 m2/g-1, which was 1.91 times more than the original surface area of unmodified BC. A-TiO2/BC also exhibited abundant hydroxyl and oxygen-containing functional groups, thereby provided adequately active sites for NOR adsorption. R2 values obtained from NOR isotherm adsorption models descended in order of Freundlich < Temkin < Sips < Langmuir, which indicated that the NOR removal by A-TiO2/BC mainly complied with monolayer adsorption accompanied by heterogeneous surface adsorption. Under weakly acidic conditions, NOR adsorption benefits from the synergistic physicochemical interactions of A-TiO2 and BC. Notably, A-TiO2/BC demonstrated an impressive NOR adsorption capacity of up to 78.14 mg g-1, with a dosage of 20 mg L-1 at 25 °C under pH 6. Such A-TiO2 modified biochar thus presents a promising alternative for NOR removal.

Photochemically induced aging of polystyrene nanoplastics and its impact on norfloxacin adsorption behavior.

The co-occurrence of nanoplastics (NPs) and antibiotics in the environment is a growing concern for ecological safety. As NPs age in natural environments, their surface properties and morphology may change, potentially affecting their interactions with co-contaminants such as antibiotics. It is crucial to understand the effect of aging on NPs adsorption of antibiotics, but detailed studies on this topic are still scarce. The study utilized the photo-Fenton-like reaction to hasten the aging of polystyrene nanoplastics (PS-NPs). The impact of aging on the adsorption behavior of norfloxacin (NOR) was then systematically examined. The results showed a time-dependent rise in surface oxygen content and functional groups in aged PS-NPs. These modifications led to noticeable physical changes, including increased surface roughness, decreased particle size, and improved specific surface area. The physicochemical changes significantly increased the adsorption capacity of aged PS-NPs for norfloxacin. Aged PS-NPs showed 5.03 times higher adsorption compared to virgin PS-NPs. The adsorption mechanism analysis revealed that in addition to the electrostatic interactions, van der Waals force, hydrogen bonding, π-π* interactions and hydrophobic interactions observed with virgin PS-NPs, aged PS-NPs played a significant role in polar interactions and pore-filling mechanisms. The study highlights the potential for aging to worsen antibiotic risk in contaminated environments. This study not only enhances the comprehension of the environmental behavior of aged NPs but also provides a valuable basis for developing risk management strategies for contaminated areas.

Discovery of indolylacryloyl-derived oxacins as novel potential broad-spectrum antibacterial candidates.

The emergence of serious bacterial resistance towards clinical oxacins poses a considerable threat to global public health, necessitating the development of novel structural antibacterial agents. Seven types of novel indolylacryloyl-derived oxacins (IDOs) were designed and synthesized for the first time from commercial 3,4-difluoroaniline via an eight-step procedure. The synthesized compounds were characterized by modern spectroscopic techniques. All target molecules were evaluated for antimicrobial activities. Most of the prepared IDOs showed a broad antibacterial spectrum and strong activities against the tested strains, especially ethoxycarbonyl IDO 10d (0.25-0.5 µg/mL) and hydroxyethyl IDO 10e (0.25-1 µg/mL) exhibited much superior antibacterial efficacies to reference drug norfloxacin. These highly active IDOs also displayed low hemolysis, cytotoxicity and resistance, as well as rapid bactericidal capacity. Further investigations indicated that ethoxycarbonyl IDO 10d and hydroxyethyl IDO 10e could effectively reduce the exopolysaccharide content and eradicate the formed biofilm, which might delay the development of drug resistance. Preliminary exploration of the antibacterial mechanism revealed that active IDOs could not only destroy membrane integrity, resulting in changes in membrane permeability, but also promote the accumulation of reactive oxygen species, leading to the production of malondialdehyde and decreased bacterial metabolism. Moreover, they exhibited the capability to bind with DNA and DNA gyrase, forming supramolecular complexes through various noncovalent interactions, thereby inhibiting DNA replication and causing bacterial death. All the above results suggested that the newly developed indolylacryloyl-derived oxacins should hold great promise as potential multitargeting broad-spectrum antibacterial candidates to overcome drug resistance.

Hydrazyl hydroxycoumarins as new potential conquerors towards Pseudomonas aeruginosa.

A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 µg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.

Ecological and human health risk assessment of pharmaceutical compounds in the Sirsa River of Indian Himalayas.

The Baddi-Barotiwala-Nalagarh (BBN) region of Indian Himalayas is one of the most important pharmaceutical industrial clusters in Asia. This study investigated the distribution, and ecological and human health risks of four most frequently used pharmaceuticals [ciprofloxacin (CIP), norfloxacin (NOR), cetirizine (CTZ) and citalopram oxalate (ECP)] when co-occurring with metal ions in the Sirsa river water of the BBN region. The concentration range of the selected pharmaceuticals was between 'not detected' to 50 µgL-1 with some exception for CIP (50-100 µgL-1) and CTZ (100-150 µgL-1) in locations directly receiving wastewater discharges. A significant correlation was found between the occurrences of NOR and Al (r2 = 0.65; p = 0.01), and CTZ and K (r2 = 0.50; p = 0.01) and Mg (r2 = 0.50; p = 0.01). A high-level ecological risk [risk quotient (RQ) > 1] was observed for algae from all the pharmaceuticals. A medium-level risk (RQ = 0.01-0.1) was observed for Daphnia from CIP, NOR and ECP, and a high-level risk from CTZ. A low-level risk was observed for fishes from CIP and NOR, whereas CTZ and ECP posed a high-level risk to fishes. The overall risk to ecological receptors was in the order: CTZ > CIP > ECP > NOR. Samples from the river locations receiving water from municipal drains or situated near landfill and pharmaceutical factories exhibited RQ > 1 for all pharmaceuticals. The average hazard quotient (HQ) values for the compounds followed the order: CTZ (0.18) > ECP (0.15) > NOR (0.001) > CIP (0.0003) for children (0-6 years); ECP (0.49) > CTZ (0.29) > NOR (0.005) > CIP (0.001) for children (7-17 years), and ECP (0.34) > CTZ (0.21) > NOR (0.007) > CIP (0.001) for adults (>17 years). The calculated risk values did not readily confirm the status of water as safe or unsafe because the values of predicted no-effect concentration (PNEC) would depend on various other environmental factors such as quality of the toxicity data, and species sensitivity and distribution, which warrants further research.