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Ecotoxicology and Environmental Safety Jun 2023Understanding the adsorption behavior of antibiotic molecules on minerals is crucial for determining the environmental fate and transport of antibiotics in soils and...
Understanding the adsorption behavior of antibiotic molecules on minerals is crucial for determining the environmental fate and transport of antibiotics in soils and waters. However, the microscopic mechanisms that govern the adsorption of common antibiotics, such as the molecular orientation during the adsorption process and the conformation of sorbate species, are not well understood. To address this gap, we conducted a series of molecular dynamics (MD) simulations and thermodynamics analyses to investigate the adsorption of two typical antibiotics, tetracycline (TET) and sulfathiazole (ST), on the surface of montmorillonite. The simulation results indicated that the adsorption free energy ranged from - 23 to - 32 kJ·mol, and - 9 to - 18 kJ·mol for TET and ST, respectively, which was consistent with the measured difference of sorption coefficient (K) for TET-montmorillonite of 11.7 L·g and ST-montmorillonite of 0.014 L·g. The simulations also found that TET was adsorbed through dimethylamino groups (85% in probability) with a molecular conformation vertical to the montmorillonite's surface, while ST was adsorbed through sulfonyl amide group (95% in probability) with vertical, tilted and parallel conformations on the surface. The results confirmed that molecular spatial orientations could affect the adsorption capacity between antibiotics and minerals. Overall, the microscopic adsorption mechanisms revealed in this study provide critical insights into the complexities of antibiotics adsorption to soil and facilitate the prediction of adsorption capacity of antibiotics on minerals and their environmental transport and fate. This study contributes to our understanding of the environmental impacts of antibiotic usage and highlights the importance of considering molecular-level processes when assessing the fate and transport of antibiotics in the environment.
Topics: Anti-Bacterial Agents; Clay; Bentonite; Minerals; Soil; Tetracycline; Sulfathiazole; Aluminum Silicates
PubMed: 37148753
DOI: 10.1016/j.ecoenv.2023.114970 -
Applied and Environmental Microbiology Oct 2023While the evolution of antimicrobial resistance is well studied in free-living bacteria, information on resistance development in dense and diverse biofilm communities...
While the evolution of antimicrobial resistance is well studied in free-living bacteria, information on resistance development in dense and diverse biofilm communities is largely lacking. Therefore, we explored how the social interactions in a duo-species biofilm composed of the brewery isolates and influence the adaptation to the broad-spectrum antimicrobial sulfathiazole. Previously, we showed that the competition between these brewery isolates enhances the antimicrobial tolerance of . Here, we found that this enhanced tolerance in duo-species biofilms is associated with a strongly increased antimicrobial resistance development in . Whereas was not able to evolve resistance against sulfathiazole in monospecies conditions, it rapidly evolved resistance in the majority of the duo-species communities. Although the initial presence of was thus required for to acquire resistance, the resistance mechanisms did not depend on the presence of . Whole genome sequencing of resistant clones showed no clear mutational hot spots. This indicates that the acquired resistance phenotype depends on complex interactions between low-frequency mutations in the genetic background of the strains. We hypothesize that the increased tolerance in duo-species conditions promotes resistance by enhancing the selection of partially resistant mutants and opening up novel evolutionary trajectories that enable such genetic interactions. This hypothesis is reinforced by experimentally excluding potential effects of increased initial population size, enhanced mutation rate, and horizontal gene transfer. Altogether, our observations suggest that the community mode of life and the social interactions therein strongly affect the accessible evolutionary pathways toward antimicrobial resistance.IMPORTANCEAntimicrobial resistance is one of the most studied bacterial properties due to its enormous clinical and industrial relevance; however, most research focuses on resistance development of a single species in isolation. In the present study, we showed that resistance evolution of brewery isolates can differ greatly between single- and mixed-species conditions. Specifically, we observed that the development of antimicrobial resistance in certain species can be significantly enhanced in co-culture as compared to the single-species conditions. Overall, the current study emphasizes the need of considering the within bacterial interactions in microbial communities when evaluating antimicrobial treatments and resistance evolution.
Topics: Anti-Infective Agents; Biofilms; Bacteria; Phenotype; Sulfathiazoles; Anti-Bacterial Agents
PubMed: 37819078
DOI: 10.1128/aem.01155-23 -
ACS Omega Dec 2023The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a...
Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure-Activity Relationship, Kinetics Mechanism, and In Silico Studies.
The search for novel drug scaffolds that can improve effectiveness and safety through drug conjugates is a promising approach. Consequently, drug conjugates constitute a dynamic field of study and advancement within medicinal chemistry. This research demonstrates the conjugation of diclofenac and mefenamic acid with sulfa drugs and their screening for urease inhibition. These conjugates' structural confirmation was performed using elemental analysis and spectroscopic methods, including IR, H NMR, and C NMR. Diclofenac conjugated with sulfanilamide (4), sulfacetamide (10), and mefenamic acid conjugated with sulfanilamide (12), and sulfamethoxazole (17) was found potent and demonstrated urease inhibition competitively, with IC (μM) values 3.59 ± 0.07, 5.49 ± 0.34, 7.92 ± 0.27, and 8.35 ± 0.26, respectively. Diclofenac conjugated with sulfathiazole (6), sulfamerazine (8), and sulfaguanidine (11), while mefenamic acid conjugated with sulfisoxazole (13), sulfathiazole (14), and sulfadiazine (15) exhibited a mixed mode of urease inhibition. The IC (μM) values were 16.19 ± 0.21, 9.50 ± 0.28, 4.35 ± 0.23, 15.86 ± 0.25, 14.80 ± 0.27, and 7.92 ± 0.27, respectively. Furthermore, molecular docking studies were employed to predict the binding pose of competitive inhibitors at the urease active site. These conjugates generated stable complexes with the urease protein observed through molecular dynamics (MD) simulations, where no conformational changes occurred throughout the simulations. These results highlight the potential for approved therapeutic molecule conjugates to give rise to new categories of pharmacological agents for urease inhibition. The structural similarity of sulfonamides with urea allows them to compete with urea for binding to the active site of the urease enzyme. Sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) can interact hydrophobically with the active site of the urease enzyme, which may disturb its structure and catalytic activity. Therefore, these conjugates may be helpful in the development of novel pharmacological agents for the treatment of a variety of illnesses in which the urease enzyme is involved.
PubMed: 38075833
DOI: 10.1021/acsomega.3c07275 -
ACS Omega Nov 2023A combined study using the surface-enhanced Raman scattering (SERS) technique and quantum chemical calculations was carried out to elucidate the adsorption behavior of...
A combined study using the surface-enhanced Raman scattering (SERS) technique and quantum chemical calculations was carried out to elucidate the adsorption behavior of sulfathiazole, an antibiotic drug, on gold nanoparticles. The tetrahedral Au cluster was used as a simple model to mimic a nanostructured gold surface. Computations using density functional theory with the PBE functional were performed in both the gas phase and aqueous medium using a continuum model. The drug is found to bind to the Au metals via the nitrogen of the thiazole ring. The interaction is also partially stabilized by the ring-surface π coupling rather than a sideway adsorption as previously proposed. In an aqueous solution, the drug molecule mainly exists as a deprotonated form, which gives rise to a much greater affinity toward Au nanoparticles as compared to the neutral forms. The drug adsorption further induces a significant alteration on the energy gap of the gold cluster Au, which could result in an electrical noise. Notable SERS signals below 1600 cm, which result from a coupling of several vibrations including the ring breathing, C-C stretching, and N-H bending, could be employed for both qualitative and quantitative detection and assessment of sulfathiazole at trace concentrations.
PubMed: 38027349
DOI: 10.1021/acsomega.3c01477 -
Journal of Food Protection Jun 2024The use of antibiotics in agriculture and livestock poses health risks to consumers. Treatments such as High Hydrostatic Pressure (HHP) have been shown to reduce...
The use of antibiotics in agriculture and livestock poses health risks to consumers. Treatments such as High Hydrostatic Pressure (HHP) have been shown to reduce antibiotic and pesticide residues in food. This study aims to investigate the matrix effect on the effectiveness of HHP on hydrochloride tetracycline (HTC) and sulfathiazole (STZ) residues in spiked food matrices. The effect of viscosity, as well as carbohydrate, protein, and fat content on the effectiveness of HHP on antibiotic residues, was investigated. The studied matrices were full-fat and fat-free bovine milk and model food systems consisting of aqueous solutions of sugars, aqueous solutions of proteins, and oil in water emulsions. Model food systems were also used to study the viscosity effect. These systems consisted of aqueous solutions of honey, aqueous solutions of apple puree, and aqueous solutions of glycerol. The HHP processing (580 MPa, 6 min, 25 °C) took place under industrial conditions. For both antibiotics, the concentration of sugars and proteins was found to affect the effectiveness of treatment. The concentration of oils affected treatment efficacy only for HTC. Reduction of antibiotics by HHP was also affected by the type of carbohydrate and the viscosity. In conclusion, the composition and the viscosity of the food matrix exert a variable effect on the studied antibiotic residues reduction by HHP indicating different underlying mechanisms of the interactions between food constituents and antibiotics under the same process conditions.
Topics: Anti-Bacterial Agents; Hydrostatic Pressure; Animals; Humans; Cattle; Viscosity; Food Contamination; Milk; Drug Residues
PubMed: 38631420
DOI: 10.1016/j.jfp.2024.100278 -
Molecules (Basel, Switzerland) Jul 2023The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a...
New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.
The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.
Topics: Molecular Docking Simulation; Flurbiprofen; Ibuprofen; Enzyme Inhibitors; Sulfacetamide; Kinetics; Urease; Sulfamerazine; Canavalia; Structure-Activity Relationship; Sulfanilamide; Sulfonamides; Molecular Structure
PubMed: 37513261
DOI: 10.3390/molecules28145389 -
Antibiotics (Basel, Switzerland) Feb 2024The presence of antibiotics in the environmental matrix has raised concerns regarding their risk to the aquatic ecosystem and human health. Surface water, such as...
The presence of antibiotics in the environmental matrix has raised concerns regarding their risk to the aquatic ecosystem and human health. Surface water, such as rivers, plays a pivotal role in the dispersion and transport of antibiotic residues. The effective monitoring of these contaminants requires investigating their sources and distribution. While numerous studies have been conducted globally to comprehend the emergence, prevalence, and management of these substances, the investigation of therapeutic antibiotics in Africa remains notably underrepresented. Consequently, data regarding these emerging contaminants in the African aquatic environments are scarce, warranting further exploration. This study aims to investigate the occurrence of four specific therapeutic antibiotics-tetracycline, sulfathiazole, penicillin g, and erythromycin-across different seasons in the Msunduzi River, Eastern South Africa. Three sampling campaigns were conducted during spring, autumn, and winter to assess the presence of these antibiotics in the river. Analyte extraction from water samples was achieved through solid-phase extraction, and quantification was performed using liquid chromatography-mass spectrometry. The findings reveal notable concentrations of these antibiotics in the river at locations closest to a wastewater treatment discharge point. Among the antibiotics studied, tetracycline (158.42-1290.43 ng/L) and sulfathiazole (112.68-1151.25 ng/L) were the most frequently detected compounds across the majority of the sampling sites and tributaries of the river. Erythromycin was less frequently detected in the surface water and wastewater effluent but was found to be a risk to algal species within the river. While wastewater effluents represent a significant source of antibiotic contamination in the river, tributaries from industrial areas and informal settlements were identified as continuous sources of antibiotic pollution. Thus, it is imperative to implement appropriate monitoring protocols to mitigate antibiotic pollution in the aquatic environment.
PubMed: 38391560
DOI: 10.3390/antibiotics13020174 -
Frontiers in Chemistry 2023Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making...
Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse effects and enhance results. Making use of this multi-target approach, a series of naproxen-sulfa drug conjugates was designed and synthesized. The newly designed conjugates were confirmed by spectroscopic techniques like IR, HNMR, CNMR, and elemental analysis. The conjugates were screened for anti-inflammatory, urease, and cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, and sulfaguanidine was found potent and showed a competitive mode of urease inhibition, with IC (µM) values 6.69 ± 0.11, 5.82 ± 0.28, 5.06 ± 0.29, respectively. When compared to other screened conjugates, the naproxen-sulfamethoxazole conjugation showed better anti-inflammatory action by inhibiting induced edema by 82.8%, which is comparable to the medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition of COX-2 at 10 µM concentration which is comparable with the reference drug (celecoxib, 77.1% inhibition). Moreover, the binding modes of competitive inhibitors with the urease and COX-2 receptor were predicted through molecular docking studies and their stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and there were no conformational changes that occurred during simulation. The obtained results showed that the conjugates of approved therapeutic molecules may lead to the development of novel types of pharmacological agents in the treatment of several pathological disorders where urease and COX-2 enzymes are involved.
PubMed: 37601915
DOI: 10.3389/fchem.2023.1206380 -
Environmental Science and Pollution... Nov 2023Sulfonamides circulating in the environment lead to disturbances in food chains and local ecosystems, but most importantly contribute to development of resistance genes,...
Sulfonamides circulating in the environment lead to disturbances in food chains and local ecosystems, but most importantly contribute to development of resistance genes, which generate problems with multidrug-resistant bacterial infections treatment. In urban areas, sources of sulfonamide distribution in soils have received comparatively less attention in contrast to rural regions, where animal-derived manure, used as a natural fertilizer, is considered the main source. The aim of this study was to determine eight sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine, sulfamethizole, sulfamethoxazole, sulfapyridine, sulfathiazole, and sulfisoxazole) in environmental soil samples collected from urbanized regions in Silesian Voivodeship with increased animal activity. These soils were grouped according to the organic carbon content. It was necessary to develop versatile and efficient extraction and determination method to analyze selected sulfonamides in various soil types. The developed LC-MS/MS method for sulfonamides analyzing was validated. The obtained recoveries exceeded 45% for soil with medium organic carbon content and 88% for sample with a very low organic carbon content (arenaceous quartz). The obtained results show the high impact of organic matter on analytes adsorption in soil, which influences recovery. All eight sulfa drugs were determined in environmental samples in the concentration range 1.5-10.5 ng g. The transformation products of the analytes were also identified, and 29 transformation products were detected in 24 out of 27 extracts from soil samples.
Topics: Animals; Sulfonamides; Soil; Chromatography, Liquid; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Poland; Ecosystem; Sulfanilamide; Carbon; Anti-Bacterial Agents
PubMed: 37843710
DOI: 10.1007/s11356-023-30146-y