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Brazilian Journal of Microbiology :... Mar 2024Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities....
Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 μg/mL and 128 μg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 μg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.
Topics: Humans; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Molecular Docking Simulation; Chromones; Escherichia coli; Schiff Bases; Anti-Bacterial Agents; Sulfanilamide; Ampicillin; Sulfonamides; Microbial Sensitivity Tests
PubMed: 38066229
DOI: 10.1007/s42770-023-01194-w -
The Science of the Total Environment Jan 2024Charge-assisted hydrogen bond (CAHB) is a key mechanism that affects the environmental behavior of pharmaceutical pollutants (PCs). However, the strength and stability...
Charge-assisted hydrogen bond (CAHB) is a key mechanism that affects the environmental behavior of pharmaceutical pollutants (PCs). However, the strength and stability of various CAHBs, and their effects on the co-sorption behavior of PCs are still unclear. Herein, DFT calculation with different solvent models including two implicit solvent model (PCM and SMD), and one explicit solvent model (ESM) were applied in this study, to investigate the effects of different CAHBs on the sorption and co-sorption behavior of four PCs (e.g., clofibric acid, p-aminobenzoic acid, acetaminophen, and sulfamerazine) on three model carbonaceous materials. First, the appearance of new peaks in the very low field of H NMR, and the blue shift of OH and NH peaks in FTIR indicated that CAHBs were indeed formed between PCs and carbonaceous materials. Next, according to the principal component analysis and correlation analysis of parameters (e.g., ΔE, bond length, bond angle, E, and ΔG) of these CAHBs calculated by the DFT with different solvent models, the results showed that SMD is the optimal model for calculating the strength and stability of CAHBs by DFT, and the strength and stability of CAHBs formed between PCs and carbonaceous materials in this study were in the order of homonuclear [O⋯H⋯O] CAHB > heteronuclear [O⋯HN]/[N⋯HO] type of CAHB > homonuclear [N⋯H⋯N]. Also, the co-sorption behavior of different PCs co-existing in binary systems further confirmed that, all above types of CAHBs formed between PCs and carbonaceous materials can produce obvious competition effect on the co-existing PCs that only OHB formed between them. This study not only reveals the environmental behavior of co-existing PCs, but also provides a theoretical basis for the design of obligate sorption materials for PCs in the natural environment.
PubMed: 37952672
DOI: 10.1016/j.scitotenv.2023.168375 -
Biochemical and Biophysical Research... Nov 2023The environmental and health risks associated with sulfonamide antibiotics (SAs) are receiving increasing attention. Through multi-spectroscopy, density functional...
The environmental and health risks associated with sulfonamide antibiotics (SAs) are receiving increasing attention. Through multi-spectroscopy, density functional theory (DFT), and molecular docking, this study investigated the interaction features and mechanisms between six representative SAs and human serum albumin (HSA). Multi-spectroscopy analysis showed that the six SAs had significant binding capabilities with HSA. The order of binding constants at 298 K was as follows: sulfadoxine (SDX): 7.18 × 10 L mol > sulfamethizole (SMT): 6.28 × 10 L mol > sulfamerazine (SMR): 2.70 × 10 L mol > sulfamonomethoxine (SMM): 2.54 × 10 L mol > sulfamethazine (SMZ): 3.06 × 10 L mol > sulfadimethoxine (SDM): 2.50 × 10 L mol. During the molecular docking process of the six SAs with HSA, the binding affinity range is from -7.4 kcal mol to -8.6 kcal mol. Notably, the docking result of HSA-SDX reached the maximum of -8.6 kcal mol, indicating that SDX may possess the highest binding capacity to HSA. HSA-SDX binding, identified as a static quenching and exothermic process, is primarily driven by hydrogen bonds (H bonds) or van der Waals (vdW) interactions. The quenching processes of SMR/SMZ/SMM/SDX/SMT to HSA are a combination of dynamic and static quenching, indicating an endothermic reaction. Hydrophobic interactions are primarily accountable for SMR/SMZ/SMM/SDX/SMT and HSA binding. Competition binding results revealed that the primary HSA-SAs binding sites are in the subdomain IB of the HAS structure, consistent with the results of molecule docking. The correlation analysis based on DFT calculations revealed an inherent relationship between the structural chemical features of SAs and the binding performance of HSA-SAs. The dual descriptor (DD) and the electrophilic Fukui function were found to have a significant relationship (0.71 and -0.71, respectively) with the binding constants of HSA-SAs, predicting the binding performance of SAs and HSA. These insights have substantial scientific value for evaluating the environmental risks of SAs as well as understanding their impact on biological life activities.
Topics: Humans; Serum Albumin, Human; Molecular Docking Simulation; Serum Albumin; Density Functional Theory; Sulfonamides; Protein Binding; Spectrometry, Fluorescence; Binding Sites; Anti-Bacterial Agents; Sulfanilamide; Circular Dichroism; Thermodynamics
PubMed: 37862782
DOI: 10.1016/j.bbrc.2023.10.040 -
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 -
Spectrochimica Acta. Part A, Molecular... Jan 2024Sulfa drugs are frequently used to treat infections, particularly in antibiotic resistant people. There are several techniques available to determine sulfa drugs,...
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, linear correlations ranging from 0.9903 to 0.9972, limits of detection 0.0030 to 0.0082 µg mL, 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.
PubMed: 37683435
DOI: 10.1016/j.saa.2023.123336 -
International Journal of Biological... Dec 2023Acid hydrotropes was considered a green medium for efficient wood fractionation at mild conditions. This study reported a comparative study on the dissolution of lignin...
Acid hydrotropes was considered a green medium for efficient wood fractionation at mild conditions. This study reported a comparative study on the dissolution of lignin in different acid hydrotropes, including p-toluenesulfonic acid (p-TsOH), 4-hydroxybenzenesulfonic acid (4-HSA), 5-sulfosalicylic acid (5-SSA), and maleic acid (MA). Under identical treatment conditions (80 °C, 60 min, and 70 % acid concentration), the removal of wood lignin varied significantly among four acid hydrotropes, 4-HSA exhibited the highest removal rate at 88.0 %, followed by p-TsOH at 81.2 %, 5-SSA at 51.1 %, and MA at 26.2 %. The molecular mechanism of the lignin dissolution was analyzed by quantum chemistry (QC) calculation and molecular dynamics (MD) simulation. The higher absorb free energy (E(absorb)) of the 4-HSA and veratrylglycerol-β-guaiacyl ether (VG) complex (E(absorb) = 17.97 kcal/mol), and the p-TsOH and VG complex (E(absorb) = 17.16 kcal/mol) contributed to a higher efficiency of lignin dissolution. Under the same level of lignin removal (~ 60 %), the four acid hydrotropes showed variations in the β-O-4 content of the extracted lignin: 4-HSA (3.1 %) < 5-SSA (10.4 %) < p-TsOH (15.9 %) < MA (63.7 %). The acidity and critical aggregation concentrations of acid hydrotropes were found to influence the content of β-O-4 bonds in the extracted lignin.
Topics: Lignin; Wood; Sulfamerazine
PubMed: 37673170
DOI: 10.1016/j.ijbiomac.2023.126696 -
Environmental Pollution (Barking, Essex... Nov 2023Sulfadiazine and its derivatives (sulfonamides, SAs) could induce distinct biotoxic, metabolic and physiological abnormalities, potentially due to their subtle...
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.
Topics: Oryza; Glycosyltransferases; Molecular Docking Simulation; Sulfanilamide; Sulfadiazine; Sulfonamides; Metabolic Diseases; Sugars
PubMed: 37669699
DOI: 10.1016/j.envpol.2023.122486 -
Environmental Science & Technology Sep 2023The spatiotemporal bioaccumulation, trophic transfer of antibiotics, and regulation of the phytoplankton biological pump were quantitatively evaluated in the Pearl...
The spatiotemporal bioaccumulation, trophic transfer of antibiotics, and regulation of the phytoplankton biological pump were quantitatively evaluated in the Pearl River, South China. The occurrence of antibiotics in organisms indicated a significant spatiotemporal trend associated with the life cycle of phytoplankton. Higher temporal bioaccumulation factors (BAFs) were found in phytoplankton at the bloom site, while lower BAFs of antibiotics in organisms could not be explained by phytoplankton biomass dilution but were attributed to the low bioavailability of antibiotics, which was highly associated with distribution coefficients ( = 0.480-0.595, < 0.05). Such lower BAFs of antibiotics in phytoplankton at higher biomass sites hampered the entry of antibiotics into food webs, and trophic dilutions were subsequently observed for antibiotics except for ciprofloxacin (CFX) and sulfamerazine (SMZ) at sites with blooms in all seasons. Distribution of CFX, norfloxacin (NFX), and sulfapyridine (SPD) showed further significant positive relationships with the plasma protein fraction ( = 0.275-0.216, < 0.05). Both mean BAFs and trophic magnification factors (TMFs) were significantly negatively correlated with phytoplankton biomass ( = 0.661-0.741, < 0.05). This study highlights the importance of the biological pump in the regulation of spatiotemporal variations in bioaccumulation and trophic transfer of antibiotics in anthropogenic-impacted eutrophic rivers in subtropical regions.
Topics: Anti-Bacterial Agents; Rivers; Bioaccumulation; Ciprofloxacin; Membrane Transport Proteins; Phytoplankton
PubMed: 37667590
DOI: 10.1021/acs.est.3c03478 -
Molecules (Basel, Switzerland) Aug 2023The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The...
The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative was formed when compound was treated with sulfamerazine. Also, compound was reacted with NH-NH in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives , , and , respectively. The results of the pharmacological study indicated that the synthesized - and derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC values of the target compounds -, and against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC values of the target compounds -, and against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC values of the target compounds -, and against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives -, and caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds - and and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds - and with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness.
Topics: Humans; Molecular Docking Simulation; COVID-19; Ivermectin; SARS-CoV-2; Sulfamerazine; Structure-Activity Relationship; Phospholipases A2, Cytosolic
PubMed: 37630304
DOI: 10.3390/molecules28166052 -
The Science of the Total Environment Nov 2023As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and...
As emerging pollutants, microplastics (MPs) and antibiotics (ATs) became a research hotspot in recent years. To evaluate the carrier effect of degradable and non-biodegradable MPs in the aquatic environment, the adsorption behaviors of polyamide (PA) and polylactic acid (PLA) towards two sulfonamide antibiotics (SAs) were investigated. Both chemical and photo-aging were used to handle the virgin MPs. Compared with PA, PLA was aged more drastically, showing the obvious grooves, notches and folds. However, due to the higher temperature during chemical aging, the tiny KPLA (PLA aged by KSO) particles were agglomerated and the specific surface area was reduced to nearly 95 %. For PA, the oxidation of chemical aging was stronger than photo-aging. After aging, the hydrophilicity and polarity of MPs increased. In the adsorption experiments, the adsorption capacity of PA towards SAs was 1.7 times higher than that of PLA. Aging process enabled the adsorption capacity of PLA increased 1.22-3.18 times. Overall, the adsorption capacity of sulfamethoxazole (SMX) by both MPs was superior to sulfamerazine (SMR). These results would help to understand the carrier effects and potential ecological risks of MPs towards co-existing contaminants.
PubMed: 37607636
DOI: 10.1016/j.scitotenv.2023.166452