Electrochemical detection of sulfanilamide using tannic acid exfoliated MoS2 nanosheets combined with reduced graphene oxide/graphite.

Sulfonamides are a family of synthetic drugs with a broad-spectrum of antimicrobial activity. Like other antimicrobials, they have been found in aquatic environments, making their detection important. Herein, an electrochemical sensor was designed using tannic acid exfoliated few-layered MoS2 sheets, which were combined with a mixture of reduced graphene oxide (rGO) and graphite flakes (G). The rGO/G was formed using electrodeposition, by cycling from -0.5 to -1.5 V in an acidified sulfate solution with well dispersed GO and G. The exfoliated MoS2 sheets were drop cast over the wrinkled rGO/G surface to form the final sensor, GCE/rGO/G/ta-MoS2. The mixture of rGO/G was superior to pure rGO in formulating the sensor. The fabricated sensor exhibited an extended linear range from 0.1 to 566 µM, with a LOD of 86 nM, with good selectivity in the presence of various salts found in water and structurally related drugs from the sulfonamide family. The sensor showed very good reproducibility with the RSD at 0.48 %, repeatability and acceptable long term stability over a 10-day period. Good recovery from both tap and river water was achieved, with recovery ranging from 90.4 to 98.9 % for tap water and from 83.5 to 94.4 % for real river water samples.

Predicting sulfanilamide solubility in the binary mixtures using a reference solvent approach.

BACKGROUND: Solubility is a fundamental physicochemical property of active pharmaceutical ingredients. The optimization of a dissolution medium aims not only to increase solubility and other aspects are to be included such as environmental impact, toxicity degree, availability, and costs. Obtaining comprehensive solubility characteristics of chemical compounds is a non-trivial and demanding process. Therefore, support from theoretical approaches is of practical importance. OBJECTIVES: This study aims to examine the accuracy of the reference solubility approach in the case of sulfanilamide dissolution in a variety of binary solvents. This pharmaceutically active substance has been extensively studied, and a substantial amount of solubility data is available. Unfortunately, using this set of data directly for theoretical modeling is impeded by noticeable inconsistencies in the published solubility data. Hence, this aspect is addressed by data curation using theoretical and experimental confirmations. MATERIAL AND METHODS: In the experimental part of our study, the popular shake-flask method combined with ultraviolet (UV) spectrophotometric measurements was applied for solubility determination. The computational phase utilized the conductor-like screening model for real solvents (COSMO-RS) approach. RESULTS: The analysis of the results of solubility calculations for sulfonamide in binary solvents revealed abnormally high error values for acetone-ethyl acetate mixtures, which were further confirmed with experimental measurements. Additional confirmation was obtained by extending the solubility measurements to a series of homologous acetate esters. CONCLUSIONS: Our study addresses the crucial issue of coherence of solubility data used for many theoretical inquiries, including parameter fitting of semi-empirical models, in-depth thermodynamic interpretations and application of machine learning protocols. The effectiveness of the proposed methodology for dataset curation was demonstrated for sulfanilamide solubility in binary mixtures. This approach enabled not only the formulation of a consistent dataset of sulfanilamide solubility binary solvent mixtures, but also its implementation as a qualitative tool guiding rationale solvent selection for experimental solubility screening.

Cotransport of microplastics and sulfanilamide antibiotics in groundwater: The impact of MP/SA ratio and aquifer media.

The aim of this study was to investigate the effects of the aquifer media, structure type, and initial concentration ratio of contaminants on the cotransport behavior of microplastics (MPs) and sulfanilamide antibiotics (SAs) through a series of one-dimensional column experiments in groundwater. Under a single suspension system, the relative mass recovery rates of fine sand, medium sand, and coarse sand were 25.65%, 37.50%, and 57.91%, respectively. The breakthrough curve of MPs showed a weak and slow upward trend, indicating that the migration of MPs in aqueous media is mainly blocked by the surface. The migration results of different structure type on SAs (ST, SM, SM2, SMX) in a single suspension system indicated that the deposition rate coefficients (kc) of the four SAs were 1.23 × 10-1, 9.09 × 10-2, 1.11 × 10-1, and 8.87 × 10-2. Under a binary suspension system (MPs:ST = 1:1), the maximum effluent concentration (MEC) of MPs in fine sand, medium sand, and coarse sand increased to 0.52, 0.64, and 0.88, respectively, and the relative mass recovery rates of ST were 22.79%, 23.59%, 20.25%. This results show that the coexistence of MPs and SAs significantly promotes the migration of MPs and inhibits that of SAs. It is mainly because of their carrier action, adsorption sites and additional deposit sites for MPs through SAs pre-deposition on media. When the initial concentration ratio was 2:1, the particles had the highest Zeta potential (-48.3 mV) and the highest potential barrier (3200 kBT), leading to the formation of complex aggregates (MPs-SAs-MPs) owing to the aggregation of colloidal MPs. The increase in the volume and number of MPs-SAs co-aggregates on the surface of the media as the initial concentration of MPs increases, which was mainly due to the disappearance of surface blocking effect and the occurrence of filtering maturation effect.

Sulfanilamide Regulates Flowering Time through Expression of the Circadian Clock Gene LUX.

Flowering time is an agriculturally important trait that can be manipulated by various approaches such as breeding, growth control and genetic modifications. Despite its potential advantages, including fine-tuning the regulation of flowering time, few reports have explored the use of chemical compounds to manipulate flowering. Here, we report that sulfanilamide, an inhibitor of folate biosynthesis, delays flowering by repressing the expression of florigen FLOWERING LOCUS T (FT) in Arabidopsis thaliana. Transcriptome deep sequencing and quantitative polymerase chain reaction analyses showed that the expression of the circadian clock gene LUX ARRYTHMO/PHYTOCLOCK1 (LUX/PCL1) is altered by sulfanilamide treatment. Furthermore, in the lux nox mutant harboring loss of function in both LUX and its homolog BROTHER OF LUX ARRHYTHMO (BOA, also named NOX), the inhibitory effect of sulfanilamide treatment on FT expression was weak and the flowering time was similar to that of the wild type, suggesting that the circadian clock may contribute to the FT-mediated regulation of flowering by sulfanilamide. Sulfanilamide also delayed flowering time in arugula (Eruca sativa), suggesting that it is involved in the regulation of flowering across Brassicaceae. We propose that sulfanilamide is a novel modulator of flowering.

Bimetallic modified halloysite particle electrode enhanced electrocatalytic oxidation for the degradation of sulfanilamide.

The treatment of antibiotics wastewater by electrocatalytic oxidation has attracted much attention. In the paper, a novel halloysite bimetallic (HLS-Cu-Mn) particle electrode material was prepared and a bench-scale electrocatalytic reaction tank was designed. A three-dimensional electrocatalytic oxidation reactor composed of HLS-Cu-Mn and a bench-scale electrocatalytic reaction tank was used to degrade Sulfanilamide (SA) wastewater. Characterization of the synthesized material was conducted with Scanning electron microscopy (SEM), X-ray polycrystalline powder diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET). The electron spin resonance spectroscopy test results confirmed that HLS-Cu-Mn produced a large number of •OH. The electrochemical workstation confirmed that HLS-Cu-Mn had strong electrocatalytic activity and repolarization ability. Under the optimum preparation conditions and degradation process parameters, the removal efficiency of SA and TOC was 99.84% and 88.95% respectively. The method also has good degradation efficiency for aniline, phenol, herbicides, antibiotics, and dyeing wastewater. It was found that 4 main intermediates appeared in the degradation process by Ultra-high performance liquid chromatography/triple tandem quadrupole mass spectrometry (LC-MS). In sum, it was believed that this work provides a new vision and idea for water treatment.

The Shapes of Sulfonamides: A Rotational Spectroscopy Study.

Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives para-toluensulfonamide and ortho-toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the 14N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for ortho-toluensulfonamide, the vibration-rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS and r0 structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation, retaining the eclipsed configuration with respect to the SO2 frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor.

A facile reaction to access novel structural sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents.

A novel type of sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents was constructed via the unique ring-opened reaction of oxiranes by imidazoles for the first time. Some developed target hybrids showed potential antimicrobial potency against the tested microbes. Especially, imidazole derivative 5f could strongly suppressed the growth of MRSA (MIC = 4 µg/mL), which was 2-fold and 16-fold more potent than the positive control sulfathiazole and norfloxacin. This compound exhibited quite low propensity to induce bacterial resistance. Antibacterial mechanism exploration indicated that compound 5f could embed in MRSA DNA to form steady 5f-DNA complex, which possibly hinder DNA replication to exert antimicrobial behavior. Molecular docking showed that molecule 5f could bind with dihydrofolate synthetase through hydrogen bonds. These results implied that imidazole derivative 5f could be served as a promising molecule for the exploration of novel antibacterial candidates.

Molecular design and preparation of 2-aminothiazole sulfanilamide oximes as membrane active antibacterial agents for drug resistant Acinetobacter baumannii.

A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line. Meanwhile, it had ability to eradicate established biofilm to alleviate the resistance burden. Mechanism investigation elucidated that compound 10c was able to disturb the membrane effectively and inhibit lactic dehydrogenase, which led to cytoplasmic content leakage. The cellular redox homeostasis was interfered via the production of reactive oxygen and nitrogen species (RONS), which further contributed to respiratory pathway inactivation and reduction of GSH activity. This work indicated that 2-aminothiazole sulfanilamide oximes could be a promising start for the exploitation of novel antibacterial agents against pathogens.

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design.

The aim of rational drug design is to develop small molecules using a quantitative approach to optimize affinity. This should enhance the development of chemical compounds that would specifically, selectively, reversibly, and with high affinity interact with a target protein. It is not yet possible to develop such compounds using computational (i.e., in silico) approach and instead the lead molecules are discovered in high-throughput screening searches of large compound libraries. The main reason why in silico methods are not capable to deliver is our poor understanding of the compound structure-thermodynamics and structure-kinetics correlations. There is a need for databases of intrinsic binding parameters (e.g., the change upon binding in standard Gibbs energy (ΔGint), enthalpy (ΔHint), entropy (ΔSint), volume (ΔVintr), heat capacity (ΔCp,int), association rate (ka,int), and dissociation rate (kd,int)) between a series of closely related proteins and a chemically diverse, but pharmacophoric group-guided library of compounds together with the co-crystal structures that could help explain the structure-energetics correlations and rationally design novel compounds. Assembly of these data will facilitate attempts to provide correlations and train data for modeling of compound binding. Here, we report large datasets of the intrinsic thermodynamic and kinetic data including over 400 primary sulfonamide compound binding to a family of 12 catalytically active human carbonic anhydrases (CA). Thermodynamic parameters have been determined by the fluorescent thermal shift assay, isothermal titration calorimetry, and by the stopped-flow assay of the inhibition of enzymatic activity. Kinetic measurements were performed using surface plasmon resonance. Intrinsic thermodynamic and kinetic parameters of binding were determined by dissecting the binding-linked protonation reactions of the protein and sulfonamide. The compound structure-thermodynamics and kinetics correlations reported here helped to discover compounds that exhibited picomolar affinities, hour-long residence times, and million-fold selectivities over non-target CA isoforms. Drug-lead compounds are suggested for anticancer target CA IX and CA XII, antiglaucoma CA IV, antiobesity CA VA and CA VB, and other isoforms. Together with 85 X-ray crystallographic structures of 60 compounds bound to six CA isoforms, the database should be of help to continue developing the principles of rational target-based drug design.

Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles.

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 µg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force.

Nocardiosis in glomerular disease patients with immunosuppressive therapy.

BACKGROUND: Glomerular disease patients have a high risk of infection, which contributes to the progression of disease per se and mortality, especially in those with long-term use of glucocorticoids and (or) immunosuppressive agents. Cases of sporadic nocardiosis have been reported in glomerular disease patients, and this observation was conducted to comprehensively understand the manifestations of and treatments for nocardiosis, which is commonly misdiagnosed as pneumonia or tuberculosis or even as lung cancer or metastatic tumors in glomerular disease patients. METHODS: We reviewed the demographic characteristics, laboratory abnormalities, radiological features, and treatments of 7 patients with nocardiosis and glomerular disease receiving steroids and immunosuppression therapy at the nephrology department of the Second Xiangya Hospital between 2012 and 2019. RESULTS: It was found that all 7 patients had been receiving methylprednisolone for renal disease at a median dose of 20 mg per day and a median duration of 4 months before developing nocardiosis. There were 4 males and 3 females, and the median age was 52.14 years. All 7 patients had hypoalbuminemia at the time of admission. In addition, various cystic abscesses in the subcutaneous tissue, with or without lung and brain involvement, were observed in these patients. Encouragingly, body temperatures returned to normal, and subcutaneous abscesses diminished or disappeared with compound sulfamethoxazole treatment alone or in combination with linezolid, imipenem and mezlocillin/sulbactam. CONCLUSIONS: It was shown that multisite abscesses, including subcutaneous, pulmonary and cerebral abscesses, were the common manifestations of nocardiosis in glomerular disease patients. Sulfonamide was the first-line antibiotic therapy for nocardiosis, and combinations of other antibiotics were also needed in some serious cases.

Stress responses and biological residues of sulfanilamide antibiotics in Arabidopsis thaliana.

Sulfonamides (SAs) are antibiotics widely used in clinical practice, livestock and poultry production, and the aquaculture industry. The compounds enter the soil environment largely through livestock and poultry manure application to farmland. SAs not only affect plant growth, but also pose a potential threat to human health through SA residues in plant tissues. In particular, sulfamethoxazole (SMZ) has been classified as a Category 3 carcinogen by the World Health Organization, and thus its soil ecological toxicity and possible health risks are of concern. Using A. thaliana as a model plant, stress responses and biological residues of sulfadiazine (SD), sulfametoxydiazine (SMD), and SMZ were investigated in the present study. Root length and aboveground plant biomass were significantly inhibited by the three types of SA, whereas lateral roots exposed to SMD grew vigorously. The contents of chlorophyll a and chlorophyll b and photosystem II maximum photochemical quantum yield declined with increase in drug concentration, which indicated that exposure to SAs affected photosynthesis and inhibited chlorophyll synthesis in A. thaliana. With increase in drug concentration, reactive oxygen species (ROS) accumulation in the leaves increased significantly. Activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were activated at low SA concentrations, but increased lipid peroxidation occurred with increase in SA concentration. Of the three compounds, SMZ was the most toxic to A. thaliana, followed by SD, and SMD was the least toxic. The results indicated that the risk of SMD entering an organism through the food chain is greater than that for SMZ and SD.

Synthesis, spectroscopic characterization, molecular docking and theoretical studies (DFT) of N-(4-aminophenylsulfonyl)-2-(4-isobutylphenyl) propanamide having potential enzyme inhibition applications.

A mutual prodrug (1) of ibuprofen and sulphanilamide has been synthesized with dual activity and improved toxicity profile. The synthesized compound has been characterized by elemental analysis, FT-IR, 1HNMR, 13CNMR and ESI-MS. The molecular geometry of the compound (1) was optimized using density functional theory (DFT/B3LYP) method with the 6-311G(d,p) basis sets in ground state. Geometric parameters (bond lengths, bond angles, torsion angles), vibrational assignments, chemical shifts and thermodynamics of the compound (1) has been calculated theoretically and compared with the experimental data. Comparative AutoDock study of compound (1) with cyclooxygenase enzymes (COX-1 and COX-2) were performed involving docking for possible selectivity of our prodrug within the two Cox enzymes. The highest binding affinities of -8.7 Kcal/mol and -8.1 Kcal/mol has been obtained for COX-1 and COX-2 enzymes respectively. Compound (1) exhibited enhanced anti-inflammatory, anti-ulcer and free radical scavenging activities as compared with the parent drugs. Based on various in vitro and in vivo tests it is suggested that the Compound (1) is more active than the parent drugs. Moreover, LD50 of compound (1) is higher than parent drug i.e. ibuprofen and sulphanilamide suggesting that the synthesized compound is much safer than its parent analogous.

Degradation of sulfanilamide by Fenton-like reaction and optimization using response surface methodology.

Excess sulfonamides are discharged into the environmental system due to the abuse of antibiotics, which threatens the ecological environment and human health. In this study, the ferric and ferrous as well as calcium peroxide (CP), sodium percarbonate (SPC) and sodium persulfate (SPS) have been used to build Fenton-like system for the sulfanilamide (SA) removal. Compared with other Fenton-like system, the Fe3+/CP system exhibited better degradation capacity and 94.65% SA was removed with 3.0 mM CP and 3.0 mM Fe3+. A response surface and corresponding quadratic regression equation were obtained by using a three-level Box-Behnken factorial design with the initial pH value and the dosage of Fe3+ and CP as the model parameters. Depended on the result of the response surface, the optimum conditions of the removal of SA in Fe3+/CP system could be obtained: [Fe3+] = 2.96 mM, [CaO2] = 2.33 mM and [pH] = 6.45. Besides that, the influences of Na+, Mg2+, Cl-, HCO3-, NO3- and HA on SA removal were also investigated under the optimum condition. The results revealed that the high concentration of HCO3- was able to inhibit degradation of SA while other ions and HA have little effect on SA degradation. These results provided a novel strategy to evaluate the catalyst/oxidant system by combining experiment and computer simulation in wastewater treatment.

Solubility advantage of sulfanilamide and sulfacetamide in natural deep eutectic systems: experimental and theoretical investigations.

Objective: The aim of this study was to explore the possibility of using natural deep eutectic solvents (NADES) as solvation media for enhancement of solubility of sulfonamides, as well as gaining some thermodynamic characteristics of the analyzed systems. Significance: Low solubility of many active pharmaceutical ingredients is a well-recognized difficulty in pharmaceutical industry, hence the need for different strategies addressing this problem. Among such strategies, those that are environmentally and economically beneficial are of particular interest. Methods: The solubility of sulfanilamide and sulfacetamide in 21 different NADES compositions comprising choline chloride with sugars or sugar alcohols was measured spectrophotometrically. Thermodynamic parameters describing the studied systems were determined using the COSMO-RS computational protocol. Results: All of the considered NADES compositions gave an increase in solubility of the studied sulfonamides, with the highest solubilities obtained for the system comprising choline chloride and glycerol in unimolar proportions, which gave a solubility advantage of 83.7 and 73.8 for sulfanilamide and sulfacetamide, respectively. Theoretical studies indicated that the dissolution of both considered sulfonamides has a low endothermic character, with the lowest enthalpy values obtained for the most optimal, i.e. unimolar, proportions. The non-monotonous trend of enthalpy of dissolution was also discussed in terms of intermolecular interactions. Conclusions: The obtained results show the feasibility of using NADES as solubility enhancers for sulfonamides and encourage for further exploration in this field.

Design, synthesis and antiproliferative evaluation of novel sulfanilamide-1,2,3-triazole derivatives as tubulin polymerization inhibitors.

Microtubule as an important target in the cancer therapy was used to design novel tubulin polymerization inhibitors. Sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and their antiproliferative activity against three selected cancer cell lines (BGC-823, MGC-803 and SGC-7901) were evaluated. All sulfanilamide-1,2,3-triazole hybrids displayed potent inhibitory activity against all cell lines. In particular, compound 10b showed the most excellent inhibitory effect against MGC-803 cells, with an IC50 value of 0.4 µM. Cellular mechanism studies elucidated that 10b induced apoptosis by decreasing the expression level of Bcl-2 and Parp and increasing the expression level of BAX. 10b inhibited the epithelial-mesenchymal transition process by up-regulating E-cadherin and down-regulating N-cadherin. Furthermore, the tubulin polymerization inhibitory activity in vitro of 10b was 2.4 µM. In vivo anticancer assay, 10b effectively inhibited MGC-803 xenograft tumor growth without causing significant loss of body weight. These sulfanilamide-1,2,3-triazole hybrids as potent tubulin polymerization inhibitors might be used as promising candidates for cancer therapy.

Modifications of Au Nanoparticle-Functionalized Graphene for Sensitive Detection of Sulfanilamide.

In this paper, we present a simple and feasible electrochemical sensor based on Au nanoparticle-functionalized graphene for the determination of sulfanilamide. Au nanoparticles were deposited on graphene, which acted as a platform to prepare excellent nanocomposites. Attributed to the graphene's large surface area and the Au nanoparticles' strong conductivity, many sulfanilamide molecules were enriched on the sensor surface and the signal response became more sensitive. Under the optimal conditions, the electrochemical sensors could be used for the efficient detection of sulfanilamide. Good linearity was observed in the range of 0.1-1000 µmol·L-1 and the detection limit was 0.011 µmol·L-1. Most importantly, the Au nanoparticle-functionalized graphene-modified electrode could be successfully applied for the detection of sulfanilamide in animal meat, and exhibited good stability, acceptable recovery, and offered a promising platform for point-of-care detecting in real samples.

Effect of Photodynamic Antibacterial Chemotherapy Combined with Antibiotics on Gram-Positive and Gram-Negative Bacteria.

The well-known and rapidly growing phenomenon of bacterial resistance to antibiotics is caused by uncontrolled, excessive and inappropriate use of antibiotics. One of alternatives to antibiotics is Photodynamic Antibacterial Chemotherapy (PACT). In the present study, the effect of PACT using a photosensitizer Rose Bengal alone and in combination with antibiotics including methicillin and derivatives of sulfanilamide synthesized by us was tested against antibiotic-sensitive and antibiotic-resistant clinical isolates of Gram-positive S. aureus and Gram-negative P. aeruginosa. Antibiotic-sensitive and resistant strains of P. aeruginosa were eradicated by Rose Bengal under illumination and by sulfanilamide but were not inhibited by new sulfanilamide derivatives. No increase in sensitivity of P. aeruginosa cells to sulfanilamide was observed upon a combination of Rose Bengal and sulfanilamide under illumination. All tested S. aureus strains (MSSA and MRSA) were effectively inhibited by PACT. When treated with sub-MIC concentrations of Rose Bengal under illumination, the minimum inhibitory concentrations (MIC) of methicillin decreased significantly for MSSA and MRSA strains. In some cases, antibiotic sensitivity of resistant strains can be restored by combining antibiotics with PACT.

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors.

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 µM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 µM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents.

Sulfanilamide in solution and liposome vesicles; in vitro release and UV-stability studies.

The main goal of this study was to develop a liposome formulation with sulfanilamide and to investigate the liposomes impact on its release and stability to the UV-A/UV-B and UV-C irradiation. Liposome dispersions with incorporated sulfanilamide were prepared by thin-film hydration method and liposomes role to the sulfanilamide release was investigated by using a dialysis method. Comparatively, sulfanilamide in phosphate buffer solution was subject to release study as well to the UV irradiation providing for the possibilities of kinetics analysis. In vitro drug release study demonstrated that 20% of sulfanilamide was released from liposomes within 1 h that is approximately twice as slower as in the case of dissolved sulfanilamide in phosphate buffer solution. The kinetic release process can be described by Korsmeyer-Peppas model and according to the value of diffusion release exponent it can be concluded that drug release mechanism is based on the phenomenon of diffusion. The sulfanilamide degradation in phosphate buffer solution and liposomes is related to the formation of UV-induced degradation products that are identified by UHPLC/MS analysis as: sulfanilic acid, aniline and benzidine. The UV-induced sulfanilamide degradation in the phosphate buffer solution and liposome vesicles fits the first- order kinetic model. The degradation rate constants are dependent on the involved UV photons energy input as well as sulfanilamide microenvironment. Liposome microenvironment provides better irradiation sulfanilamide stability. The obtained results suggest that liposomes might be promising carriers for delayed sulfanilamide delivery and may serve as a basis for further research.