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Acta Crystallographica. Section E,... Jun 2015In the title zwitterionic compound, C20H15N3O3S2, the 2-hy-droxy-naphthalene-1-carbaldehyde group A, the anilinic unit B and the 1,3-thia-zol-2(3H)-imine group C are...
In the title zwitterionic compound, C20H15N3O3S2, the 2-hy-droxy-naphthalene-1-carbaldehyde group A, the anilinic unit B and the 1,3-thia-zol-2(3H)-imine group C are each approximately planar with r.m.s. deviation of 0.0721, 0.0412 and 0.0125 Å, respectively. The dihedral angles between A/B, A/C and B/C are 24.70 (10), 79.97 (7) and 83.14 (6)°, respectively. There is an intra-molecular S(6) motif involving the imine N-H and the naphtho-late O atom. In the crystal, inversion-related mol-ecules form dimers as a result of N-H⋯N and N-H⋯O hydrogen bonds with R 2 (2)(8) and R 1 (2)(4) motifs, respectively. Weak π-π inter-actions between the benzene and naphthyl rings of inversion-related mol-ecules have ring centroid-centroid distances of 3.638 (2) and 4.041 (2) Å. A C-H⋯π inter-action occurs between the thia-zol ring and the benzene ring of an adjacent mol-ecule.
PubMed: 26090203
DOI: 10.1107/S2056989015009640 -
Journal of Molecular Biology Aug 2019Microcin B17 (MccB17) is an antibacterial peptide produced by strains of Escherichia coli harboring the plasmid-borne mccB17 operon. MccB17 possesses many notable... (Review)
Review
Microcin B17 (MccB17) is an antibacterial peptide produced by strains of Escherichia coli harboring the plasmid-borne mccB17 operon. MccB17 possesses many notable features. It is able to stabilize the transient DNA gyrase-DNA cleavage complex, a very efficient mode of action shared with the highly successful fluoroquinolone drugs. MccB17 stabilizes this complex by a distinct mechanism making it potentially valuable in the fight against bacterial antibiotic resistance. MccB17 was the first compound discovered from the thiazole/oxazole-modified microcins family and the linear azole-containing peptides; these ribosomal peptides are post-translationally modified to convert serine and cysteine residues into oxazole and thiazole rings. These chemical moieties are found in many other bioactive compounds like the vitamin thiamine, the anti-cancer drug bleomycin, the antibacterial sulfathiazole and the antiviral nitazoxanide. Therefore, the biosynthetic machinery that produces these azole rings is noteworthy as a general method to create bioactive compounds. Our knowledge of MccB17 now extends to many aspects of antibacterial-bacteria interactions: production, transport, interaction with its target, and resistance mechanisms; this knowledge has wide potential applicability. After a long time with limited progress on MccB17, recent publications have addressed critical aspects of MccB17 biosynthesis as well as an explosion in the discovery of new related compounds in the thiazole/oxazole-modified microcins/linear azole-containing peptides family. It is therefore timely to summarize the evidence gathered over more than 40 years about this still enigmatic molecule and place it in the wider context of antibacterials.
Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteria; Bacteriocins; Cinoxacin; DNA Cleavage; DNA Gyrase; Drug Development; Drug Resistance, Microbial; Escherichia coli; Fluoroquinolones; Humans; Mutation; Nitro Compounds; Peptides; Protein Processing, Post-Translational; Thiazoles; Toxins, Biological
PubMed: 31181289
DOI: 10.1016/j.jmb.2019.05.050 -
Toxics Apr 2022Veterinary antibiotics (VAs) released into the environment are a concern because of the possibility for increasing antibiotic-resistance genes. The concentrations of six...
Veterinary antibiotics (VAs) released into the environment are a concern because of the possibility for increasing antibiotic-resistance genes. The concentrations of six VAs, chlortetracycline, oxytetracycline, tetracycline, sulfamethazine, sulfamethoxazole, and sulfathiazole, in manure-based compost, soil, and crops were measured using liquid chromatography-tandem mass spectrometry. Mass balance analysis was conducted based on the measured antibiotic concentration, cultivation area, and amount of manure-based compost applied. The result showed that the detected mean concentration of VAs ranges was 3.52~234.19 μg/kg, 0.52~13.08 μg/kg, and 1.05~39.57 μg/kg in manure-based compost, soil, and crops, respectively, and the substance of VAs detected in different media was also varied. Mass balance analysis showed that the VAs released from the manure-based compost can remain in soil (at rates of 26% to 100%), be taken up by crops (at rates of 0.4% to 3.7%), or dissipated (at rates of 9% to 73%) during the cultivation period. Among the six VAs, chlortetracycline and oxytetracycline mainly remained in the soil, whereas sulfamethoxazole and sulfathiazole were mainly dissipated. Although we did not verify the exact mechanism of the fate and distribution of VAs in this study, our results showed that these can vary depending on the different characteristics of VAs and the soil properties.
PubMed: 35622627
DOI: 10.3390/toxics10050213 -
Biochemistry Research International 2021Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result,...
Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72-81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their antibacterial activity against two Gram-negative ( and ) and two Gram-positive bacterial strains ( and ) by disk diffusion method. Among synthesized compounds, compound showed potent inhibitory activity against Gram-negative, with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound showed the strongest activity with IC values of 1.655 g/mL. The synthesized compounds were evaluated for their molecular docking analysis using gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from -7.8 to -10.0 kcal/mol with 2XCT and -7.5 to -9.7 with 1DNU. Compound showed very good binding score -9.7 kcal/mol with both of the proteins and had promising alignment with results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6-31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.
PubMed: 34950517
DOI: 10.1155/2021/7534561 -
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 -
Molecules (Basel, Switzerland) May 2022The sulfonamide-zinc ion interaction, performing a key role in various biological contexts, is the focus of the present study, with the aim of elucidating ligation...
The sulfonamide-zinc ion interaction, performing a key role in various biological contexts, is the focus of the present study, with the aim of elucidating ligation motifs in zinc complexes of sulfa drugs, namely sulfadiazine (SDZ) and sulfathiazole (STZ), in a perturbation-free environment. To this end, an approach is exploited based on mass spectrometry coupled with infrared multiple photon dissociation (IRMPD) spectroscopy backed by quantum chemical calculations. IR spectra of Zn(HO+SDZ-H) and Zn(HO+STZ-H) ions are consistent with a three-coordinate zinc complex, where ZnOH binds to the uncharged sulfonamide via N(heterocycle) and O(sulfonyl) donor atoms. Alternative prototropic isomers Zn(OH)(SDZ-H) and Zn(OH)(STZ-H) lie 63 and 26 kJ mol higher in free energy, respectively, relative to the ground state Zn(OH)(SDZ) and Zn(OH)(STZ) species and do not contribute to any significant extent in the sampled population.
Topics: Ions; Spectrophotometry, Infrared; Sulfanilamide; Sulfonamides; Zinc
PubMed: 35630621
DOI: 10.3390/molecules27103144 -
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 -
Membranes Feb 2022Carbon nanodots (CNDs)-embedded pullulan (PUL) nanofibers were developed and successfully applied for sulfathiazole (STZ) removal from wastewater streams for the first...
Carbon nanodots (CNDs)-embedded pullulan (PUL) nanofibers were developed and successfully applied for sulfathiazole (STZ) removal from wastewater streams for the first time. The CNDs were incorporated into PUL at 0.0%, 1.0%, 2.0%, and 3.0% (/) to produce M1, M2, M3, and M4 nanofibers (PUL-NFs), respectively. The produced PUL-NFs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), thermal gravimetric analysis (TGA) and Differential scanning calorimetry (DSC) and applied for STZ removal from aqueous solutions through pH, kinetics, and equilibrium batch sorption trials. A pH range of 4.0-6.0 was observed to be optimal for maximum STZ removal. Pseudo-second order, intraparticle diffusion, and Elovich models were suitably fitted to kinetics adsorption data ( = 0.82-0.99), whereas Dubinin-Radushkevich, Freundlich, and Langmuir isotherms were fitted to equilibrium adsorption data ( 0.88-0.99). STZ adsorption capacity of PUL-NFs improved as the amount of embedded CNDs increased. Maximum STZ adsorption capacities of the synthesized PUL-NFs were in the order of: M4 > M3 > M2 > M1 (133.68, 124.27, 93.09, and 35.04 mg g, respectively). Lewis acid-base reaction and π-π electron donor-acceptor interactions were the key STZ removal mechanisms under an acidic environment, whereas H-bonding and diffusion were key under a basic environment. Therefore, CNDs-embedded PUL-NFs could be employed as an environmentally friendly, efficient, and non-toxic adsorbent to remove STZ from wastewater streams.
PubMed: 35207149
DOI: 10.3390/membranes12020228 -
Microbiology Spectrum Dec 2022Quorum sensing (QS) is a cell-density-dependent, intercellular communication system mediated by small diffusible signaling molecules. QS regulates a range of bacterial...
Quorum sensing (QS) is a cell-density-dependent, intercellular communication system mediated by small diffusible signaling molecules. QS regulates a range of bacterial behaviors, including biofilm formation, virulence, drug resistance mechanisms, and antibiotic tolerance. Enzymes capable of degrading signaling molecules can interfere in QS-a process termed as quorum quenching (QQ). Remarkably, previous work reported some cases where enzymatic interference in QS was synergistic to antibiotics against Pseudomonas aeruginosa. The premise of combination therapy is attractive to fight against multidrug-resistant bacteria, yet comprehensive studies are lacking. Here, we evaluate the effects of QS signal disruption on the antibiotic resistance profile of P. aeruginosa by testing 222 antibiotics and antibacterial compounds from 15 different classes. We found compelling evidence that QS signal disruption does indeed affect antibiotic resistance (40% of all tested compounds; 89/222), albeit not always synergistically (not synergistic for 19% of compounds; 43/222). For some tested antibiotics, such as sulfathiazole and trimethoprim, we were able to relate the changes in resistance caused by QS signal disruption to the modulation of the expression of key genes of the folate biosynthetic pathway. Moreover, using a P. aeruginosa-based Caenorhabditis elegans killing model, we confirmed that enzymatic QQ modulates the effects of antibiotics on P. aeruginosa's pathogenicity . Altogether, these results show that signal disruption has profound and complex effects on the antibiotic resistance profile of P. aeruginosa. This work suggests that combination therapy including QQ and antibiotics should be discussed not globally but, rather, in case-by-case studies. Quorum sensing (QS) is a cell-density-dependent communication system used by a wide range of bacteria to coordinate behaviors. Strategies pertaining to the interference in QS are appealing approaches to control microbial behaviors that depend on QS, including virulence and biofilms. Interference in QS was previously reported to be synergistic with antibiotics, yet no systematic assessment exists. Here, we evaluate the potential of combination treatments using the model opportunistic human pathogen Pseudomonas aeruginosa PA14. In this model, collected data demonstrate that QS largely modulates the antibiotic resistance profile of PA14 (for more than 40% of the tested drugs). However, the outcome of combination treatments is synergistic for only 19% of them. This research demonstrates the complex relationship between QS and antibiotic resistance and suggests that combination therapy including QS inhibitors and antibiotics should be discussed not globally but, rather, in case-by-case studies.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Pseudomonas aeruginosa; Quorum Sensing; Virulence Factors; Drug Resistance, Bacterial
PubMed: 36314960
DOI: 10.1128/spectrum.01269-22 -
Molecules (Basel, Switzerland) Jul 2019This study explores the effect of physical aging and/or crystallization on the supersaturation potential and crystallization kinetics of amorphous active pharmaceutical...
This study explores the effect of physical aging and/or crystallization on the supersaturation potential and crystallization kinetics of amorphous active pharmaceutical ingredients (APIs). Spray-dried, fully amorphous indapamide, metolazone, glibenclamide, hydrocortisone, hydrochlorothiazide, ketoconazole, and sulfathiazole were used as model APIs. The parameters used to assess the supersaturation potential and crystallization kinetics were the maximum supersaturation concentration (C), the area under the curve (AUC), and the crystallization rate constant (k). These were compared for freshly spray-dried and aged/crystallized samples. Aged samples were stored at 75% relative humidity for 168 days (6 months) or until they were completely crystallized, whichever came first. The solid-state changes were monitored with differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. Supersaturation potential and crystallization kinetics were investigated using a tenfold supersaturation ratio compared to the thermodynamic solubility using the µDISS Profiler. The physically aged indapamide and metolazone and the minimally crystallized glibenclamide and hydrocortisone did not show significant differences in their C and AUC when compared to the freshly spray-dried samples. Ketoconazole, with a crystalline content of 23%, reduced its C and AUC by 50%, with C being the same as the crystalline solubility. The AUC of aged metolazone, one of the two compounds that remained completely amorphous after storage, significantly improved as the crystallization kinetics significantly decreased. Glibenclamide improved the most in its supersaturation potential from amorphization. The study also revealed that, besides solid-state crystallization during storage, crystallization during dissolution and its corresponding pathway may significantly compromise the supersaturation potential of fully amorphous APIs.
Topics: Calorimetry, Differential Scanning; Chemical Phenomena; Crystallization; Drug Stability; Kinetics; Pharmaceutical Preparations; Preservation, Biological; Solubility; Spectrum Analysis, Raman; Time Factors
PubMed: 31357587
DOI: 10.3390/molecules24152731