Insights into the pH-dependent interactions of sulfadiazine antibiotic with soil particle models.

Sulfonamide antibiotics (SAs) are widely used as a broad-spectrum antibiotic, leading to global concerns due to their potential soil accumulation and subsequent effects on ecosystems. SAs often exhibit remarkable environmental persistence, necessitating further investigation to uncover the ultimate destiny of these molecules. In this work, molecular dynamics simulations combined with complementary quantum chemistry calculations were employed to investigate the influence of pH on the behavior of sulfadiazine (SDZ, a typical SAs) in soil particle models (silica, one of the main components of soil). Meanwhile, the quantification of SDZ molecules aggregation potential onto silica was further extended. SDZ molecules tend to form a monolayer on the soil surface under acidic conditions while forming aggregated adsorption on the surface under neutral conditions. Due to the hydrophilicity of the silica, multiple hydration layers would form on its surface, hindering the further adsorption of SDZ molecules on its surface. The calculated soil-water partition coefficient (Psoil/water) of SDZ+ and SDZ were 9.01 and 7.02, respectively. The adsorption evaluation and mechanisms are useful in controlling the migration and transformation of SAs in the soil environment. These findings provide valuable insights into the interactions between SDZ and soil components, shedding light on its fate and transport in the environment.

Synthesis, characterization of novel N-(4-cyano-1,3-oxazol-5-yl)sulfonamide derivatives and in†vitro screening their activity against NCI-60 cancer cell lines.

A novel series of N-(4-cyano-1,3-oxazol-5-yl)sulfonamides have been synthesized and characterized by IR, 1 H NMR, 13 C NMR spectroscopy, elemental analysis and chromato-mass-spectrometry. The anticancer activities of all newly synthesized compounds were evaluated via a single high-dose assay (10 µM) against 60 cancer cell lines by the National Cancer Institute (USA) according to its screening protocol. Among them, compounds 2 and 10 exhibited the highest activity against the 60 cancer cell lines panel in the one-dose assay. Compounds 2 and 10 showed inhibitory activity within the GI50 parameter and in five dose analyses. However, their cytostatic activity was only observed against some cancer cell lines, and cytotoxic concentration was outside the maximum used, i. e., >100 µM. The COMPARE analysis showed that the average graphs of the tested compounds have a moderate positive correlation with compounds with the L-cysteine analog and vinblastine (GI50 ) as well as paclitaxel (TGI), which target microtubules. Therefore, disruption of microtubule formation may be one of the mechanisms of the anticancer activity of the tested compounds, especially since among tubulin inhibitors with antitumor activity, compounds with an oxazole motif are widely represented. Therefore, N-(4-cyano-1,3-oxazol-5-yl)sulfonamides may be promising for further functionalization to obtain more active compounds.

Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors.

The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a-3p) in good to excellent yields (78%-91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic studies. Single crystal X-ray studies for 3a, 3d, and 3i verified the proposed structure. The newly developed sulfonamide-phosphonates were evaluated for their inhibitory properties against four isoforms of human carbonic anhydrase (hCA I, II, IX, and XII). The results demonstrated that they exhibited greater potency in inhibiting hCA XII compared to hCA I, II, and IX, with Ki ranging from 5.1 to 51.1 nM. Compounds 3l and 3p displayed the highest potency, exhibiting selectivity ratios of I/XII >298.7 and 8.5, and II/XII ratios of 678.1 and 142.1, respectively. Molecular docking studies were conducted to explore their binding patterns within the binding pocket of CA XII. The results revealed that the sulfonamide NH group coordinated with the Zn2+ ion, and hydrogen bond interactions were observed with residue Thr200. Additionally, hydrophobic interactions were identified between the benzenesulfonamide phenyl ring and Leu198. Compounds 3p and 3l exhibited an additional hydrogen bonding interaction with other amino acid residues. These supplementary interactions may contribute to the enhanced potency and selectivity of these compounds toward the CA XII isoform.

Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae.

IMPORTANCE: Antibiotics can induce dose-dependent hormetic effects on bacterial cell proliferation, i.e., low-dose stimulation and high-dose inhibition. However, the underlying molecular basis has yet to be clarified. Here, we showed that sulfonamides play dual roles as a weapon and signal against Comamonas testosteroni that can modulate cell physiology and phenotype. Subsequently, through investigating the hormesis mechanism, we proposed a comprehensive regulatory pathway for the hormetic effects of Comamonas testosteroni low-level sulfonamides and determined the generality of the observed regulatory model in the Comamonadaceae family. Considering the prevalence of Comamonadaceae in human guts and environmental ecosystems, we provide critical insights into the health and ecological effects of antibiotics.

Clinical characteristics of hospitalized patients with Nocardia genus detection by metagenomic next generation sequencing in a tertiary hospital from southern China.

OBJECTIVE: As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management. METHODS: A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus. RESULTS: Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually. CONCLUSION: Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.

CO2-plasma surface treatment of graphite sheet electrodes for detection of chloramphenicol, ciprofloxacin and sulphanilamide.

Graphite sheet (GS) electrodes are flexible and versatile substrates for sensing electrochemical; however, their use has been limited to incorporate (bio)chemical modifiers. Herein, we demonstrated that a cold (low temperature) CO2 plasma treatment of GS electrodes provides a substantial improvement of the electrochemical activity of these electrodes due to the increased structural defects on the GS surface as revealed by Raman spectroscopy (ID/IG ratio), and scanning electron microscopy images. XPS analyses confirmed the formation of oxygenated functional groups at the GS surface after the plasma treatment that are intrinsically related to the substantial increase in the electron transfer coefficient (K0 values increased from 1.46 × 10-6 to 2.09 × 10-3 cm s-1) and with reduction of the resistance to charge transfer (from 129.8 to 0.251 kΩ). The improved electrochemical activity of CO2-GS electrodes was checked for the detection of emerging contaminant species, such as chloramphenicol (CHL), ciprofloxacin (CIP) and sulphanilamide (SUL) antibiotics, at around + 0.15, + 1.10 and + 0.85 V (versus Ag/AgCl), respectively, by square wave voltammetry. Limit of detection values in the submicromolar range were achieved for CHL (0.08 µmol L-1), CIP (0.01 µmol L-1) and SFL (0.11 µmol L-1), which enabled the sensor to be successfully applied to natural waters and urine samples (recovery values from 85 to 119%). The CO2-GS electrode is highly stable and inexpensive ($0.09 each sensor) and can be easily inserted in portable 3D printed cells for environmental on-site analyses.

Gallic Acid Restores the Sulfonamide Sensitivity of Multidrug-Resistant Streptococcus suis via Polypharmaceology Mechanism.

Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.

Preconception use of antibiotics and fecundability: a Danish prospective cohort study.

OBJECTIVE: To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. DESIGN: SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). SETTING: Not applicable. SUBJECT(S): 9462 female participants, median age 29 years at enrollment. EXPOSURE: Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. MAIN OUTCOME MEASURE(S): Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. RESULT(S): During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. CONCLUSION(S): Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

Sulfonamide Porphyrins as Potent Photosensitizers against Multidrug-Resistant Staphylococcus aureus (MRSA): The Role of Co-Adjuvants.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 µM upon white light radiation with an irradiance of 25 mW cm-2 and a total light dose of 15 J cm-2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

Novel magnetic graphoxide/biochar composite derived from tea for multiple SAs and QNs antibiotics removal in water.

Antibiotics pollution is an urgent public health issue. Biochar is a kind of promising composite for removal antibiotic in aqueous environment. In this study, a novel magnetic graphoxide/biochar composite (mGO/TBC) was synthesized by simple impregnation method and used as an efficient and recyclable persulfate (PS) activator for degradation and removal of sulfonamides (SAs) and quinolones (QNs) antibiotics. Based on the synergism pre-adsorption and degradation between graphoxide and biochar, the removal rates of mGO/TBC on sarafloxacin hydrochloride, sulfadimethoxine, sulfapyridine, sulfadoxine, sulfamonomethoxine, sulfachloropyridazine, enrofloxacin, and ciprofloxacin were increased above 95%. Moreover, the mGO/TBC could be reused at least seven times after degradation-recovery cycles. Quenching experiment and ESR analysis proved that 1O2, •OH, and SO4•- from mGO/TBC/PS system were the primary oxidation active species to degrade SAs and QNs. It is a promising substrate for antibiotic bioremediation with good application prospects.

Comparison of conventional and dispersive solid phase extraction clean-up approaches for the simultaneous analysis of tetracyclines and sulfonamides in a variety of fresh vegetables.

The extensive use of antibiotics in agriculture has led to the occurrence of residual drugs in different vegetables frequently consumed by humans. This could pose a potential threat to human health, not only because of the possible effects after ingestion but also because the transmission of antibiotic-resistant genes could occur. In this work, two accurate sample preparation procedures were developed and validated for the simultaneous analysis of sulfonamides (SAs) and tetracyclines (TCs) in four of the most widely consumed vegetables (lettuce, onion, tomato, and carrot) in Europe. The evaluated protocols were based on QuECHERS for extraction and subsequent clean-up by SPE (solid phase extraction) or dispersive SPE. Parameters affecting both extraction and clean-up were carefully evaluated and selected for accuracy of results and minimal matrix effect. Overall, apparent recoveries were above 70% for most of the target analytes with both analytical procedures, and adequate precision (RSD<30%) was obtained for all the matrices. The procedural limits of quantification (LOQPRO) values for SPE clean-up remained below 4.4 µg kg-1 for TCs in all vegetables except for chlortetracycline (CTC) in lettuce (11.3 µg kg-1) and 3.0 µg kg-1 for SAs, with the exception of sulfadiazine (SDZ) in onion (3.9 µg kg-1) and sulfathiazole (STZ) in carrot (5.0 µg kg-1). Lower LOQPRO values (0.1-3.7 µg kg-1) were obtained, in general, when dSPE clean-up was employed. Both methods were applied to twenty-five market vegetable samples from ecological and conventional agriculture and only sulfamethazine (SMZ) and sulfapyridine (SPD) were detected in lettuce at 1.2 µg kg-1 and 0.5 µg kg-1, respectively.

Ultrasensitive evanescent wave optical fiber aptasensor for online, continuous, type-specific detection of sulfonamides in environmental water.

Sensors capable for online continuous monitoring of total sulfonamides in environmental waters are highly desired due to their adverse effects on ecosystem, unexpected concentration fluctuation, and diversity. At present, no sensor with this capability has been reported. In this study, we evaluated the cross reactivity (CR) of the previously reported sulfadimethoxine-binding aptamer using DNase I assay and found that the aptamer was type-specific to sulfonamides. We then fabricated the first type-specific sulfonamide sensor, where the aptamer was immobilized on the optical fiber of the evanescent wave sensor, followed by the surface coating with Tween 80. The competitive binding of sulfonamides and Cy5.5 labeled complementary DNA enabled the low femtomolar to picomolar sensitivity and the detection of total 14 sulfonamides spiked in the lake water. The sensor also exhibited high selectivity, regeneration capability (40 cycles), stability (65 days), and short detection time (5 min). In addition, we found that the CRs were greatly dependent on the buffer composition. By performing the parallel detections in two buffers, the sensors detected 18 out of the 24 sulfonamides with the diversity coverage higher than commercial ELISA kits. Our aptasensor fills the technical gap for continuous monitoring of total sulfonamides in environmental waters.

Eco-friendly methods of synthesis and preliminary biological evaluation of sulfonamide derivatives of cyclic arylguanidines.

The chemotype of arylsulfonamide derivatives of cyclic arylguanidines is a source of molecules with valuable biological activities, including antimicrobial and antitumor properties. The methods of the synthesis presented in the literature are characterized with low selectivity and high environmental nuisance. In this publication, we present a developed alternative and earlier undescribed pathway C, for the synthesis of arylsulfonamide derivatives of cyclic arylguanidines (N-(1H-arylimidazol-2-yl)arylsulfonamides and N-(1,4-dihydroquinazolin-2-yl)arylsulfonamides), including reaction between 2-(methylsulfanyl)-benzimidazole or 2-(methylsulfanyl)-3,4-dihydroquinazoline with arylsulfonamides. We also optimized previously reported methods; A (reaction of 2-aminobenzimidazole or 2-amino-3,4-dihydroquinazoline with arylsulfonyl chlorides) and B (reaction of dimethyl-(arylsulfonyl)carbonodithioimidate with aryldiamines). The conducted research allowed achieving two independent ecological and quick methods of obtaining the desired products. We used ecological methods of ultrasound-assisted or microwave synthesis, solvent-free reactions and a"green" reaction environment. In both pathways, it has proven advantageous to use H2O as the solvent and K2CO3 (1 or 3 equivalent) as the basic agent. In the sonochemical variant, the efficiency reached B: 37-89 %, C: 90 % in 60 min (P = 80 W and f = 40 kHz), while in the microwave synthesis it was B: 38-74 %, C: 63-85 % in 0.5-4 min (P = 50 W). Path A led to a complementary substitution product (i.e. 1-(arylsulfonyl)-1H-benzimidazol-2-amine or 1-(arylsulfonyl)-1,4-dihydroquinazolin-2-amine). We obtained a small group of compounds that were tested for cytotoxicity. The 10f (N-(1,4-dihydroquinazolin-2-yl)naphthalene-1-sulfonamide) showed cytotoxic activity towards human astrocytoma cell line 1321 N1. The calculated IC50 value was 8.22 µM at 24 h timepoint (doxorubicin suppressed 1321 N1 cell viability with IC50 of 1.1 µM). The viability of the cells exposed to 10f for 24 h dropped to 48.0 % compared to vehicle control, while the cells treated with doxorubicin experienced decline to 47.5 %. We assessed its potential usefulness in pharmacotherapy in the ADMET study, confirming its ability to cross the blood-brain barrier (Pe = 5.0 ± 1.5 × 10-6 cm/s) and the safety of its potential use in terms of DDI and hepatotoxicity.

Enhanced sulfonamides removal via microalgae-bacteria consortium via co-substrate supplementation.

Both co-cultivation and co-substrate addition strategies have exhibited massive potential in microalgae-based antibiotic bioremediation. In this study, glucose and sodium acetate were employed as co-substrate in the cultivation of microalgae-bacteria consortium for enhanced sulfadiazine (SDZ) and sulfamethoxazole (SMX) removal. Glucose demonstrated a two-fold increase in biomass production with a maximum specific growth rate of 0.63 ± 0.01 d-1 compared with sodium acetate. The supplementation of co-substrate enhanced the degradation of SDZ significantly up to 703 ± 18% for sodium acetate and 290 ± 22% for glucose, but had almost no effect on SMX. The activities of antioxidant enzymes, including peroxidase, superoxide dismutase and catalase decreased with co-substrate supplementation. Chlorophyll a was associated with protection against sulfonamides and chlorophyll b might contribute to SDZ degradation. The addition of co-substrates influenced bacterial community structure greatly. Glucose enhanced the relative abundance of Proteobacteria, while sodium acetate improved the relative abundance of Bacteroidetes significantly.

Degradation of sulfonamides in aquaculture wastewater by laccase-syringaldehyde mediator system: Response surface optimization, degradation kinetics, and degradation pathway.

As a new type of environmental pollutant, environmental antibiotic residues have attracted widespread attention, and the degradation and removal of antibiotics has become an engaging topic for scholars. In this paper, Novozym 51003 industrialized laccase and syringaldehyde were combined to degrade sulfonamides in aquaculture wastewater. Design Expert10 software was used for multiple regression analysis, and a response surface regression model was established to obtain the optimal degradation parameters. In the actual application, the degradation system could maintain a stable performance within 9 h, and timely supplement of the mediator could achieve a better continuous degradation effect. Low concentrations of heavy metals and organic matter would not significantly affect the degradation performance of the laccase-mediator system, making the degradation system suitable for a wide range of water quality. Enzymatic reaction kinetics demonstrated a strong affinity of sulfadiazine to the substrate. Ten degradation products were speculated using high-resolution mass spectrum based on the mass/charge ratios and the publication results. Four types of possible degradation pathways of sulfadiazine were deduced. This work provides a practical method for the degradation and removal of sulfonamide antibiotics in actual sewage.

Microbially-mediated synthesis of activated carbon derived from cottonseed husks for enhanced sulfanilamide removal.

This study provided a novel pathway to develop activated carbon with enhanced adsorption performance via feedstock pretreatment by fungi. The growth of Pleurotus ostreatus on cottonseed husks offered this feedstock an advantageous pore size for porous carbon making. The prepared activated carbons derived from cottonseed husks (CSH-ACs) during different fungal growth periods exhibited extraordinary performance than commercial activated carbon for sulfanilamide adsorptive removal. Their experimental data of adsorption capacities for sulfanilamide were 139.43, 146.15, and 146.16 mg g-1, respectively. The adsorption behaviors of sulfanilamide on CSH-ACs were evaluated by kinetic, isotherm and thermodynamic models. Pore filling, hydrogen-bond forming and π-π staking interactions all contributed to the rapid sulfanilamide removal. The microporous-mesoporous structure, stronger hydrophilicity, and richer functional groups moieties owing to the lignocellulose decomposition in the plant wall significantly strengthened the adsorption process on the microbial-mediated activated carbon. The effects of pH and water impurities (H2PO4-, CO32-, SO42-, Cl-, and humic acid) on sulfanilamide removal were investigated by a single factor experimental design. Results indicated that CSH-ACs were suitable for sulfanilamide removal in actual wastewater treatment with wide pH adaptability and resilience to interference.

Sulfonamide degradation and metabolite characterization in submerged membrane photobioreactors for livestock excreta treatment.

Residual veterinary antibiotics have been detected in livestock wastewater treatment plants. Despite the long retention time, antibiotic treatment efficiency has shown clear limitations. In this study, we evaluated submerged membrane photobioreactors (SMPBR) during sulfonamide antibiotic-containing livestock wastewater treatment under mixotrophic and photoautotrophic conditions. The results showed that microalgal sulfur degradation and consumption under mixotrophic conditions accelerated the biomass concentration increase to 2800 mg VSS/L compared to the 1800 mg VSS/L measured under photoautotrophic conditions. Although microalgal metabolites, such as soluble microbial products and extracellular polymeric substances, might cause membrane fouling in the SMPBR, we proved that microalgae could remove sulfonamide and release degradation-associated sulfur, along with nitrogen and phosphorus. Moreover, this study confirms the statistical correlation between metabolites and sulfonamides. In summary, the results of this study provide promising insights into antibiotic-containing livestock wastewater treatment.

Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds.

A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, 12 and 13 were demonstrated to have MICs of 0.0625 µg/mL against S. uberis in the presence of 50 µM ZnSO4. Against S. aureus compounds 9g (MIC 4 µg/mL) and 11d (MIC 8 µg/mL) showed the greatest activity, whereas all compounds were found to be inactive against E. coli (MIC > 256 µg/mL); again in the presence of 50 µM ZnSO4. All compounds were demonstrated to be significantly less active in the absence of supplementary zinc. Compound 9g was subsequently confirmed to be bactericidal, with an MBC (≥3log10 cfu/mL reduction) of 0.125 µg/mL against S. uberis in the presence of 50 µM ZnSO4. To validate the sanitising activity of compound 9g in the presence of supplementary zinc, a quantitative suspension disinfection (sanitizer) test was performed. In this preliminary test, sanitizing activity (>5log10 reduction of CFU/mL in 5 min) was observed against S. uberis for compound 9g at concentrations as low as 1 mg/mL, validating the potential of this compound to function as a topical sanitizer against the major environmental mastitis-causing microorganism S. uberis.

Polymorphism in Sulfanilamide: 14N Nuclear Quadrupole Resonance Study.

To demonstrate the selectivity of 14N nuclear quadrupole resonance (14N NQR) spectroscopy in chemistry and pharmacy, a study of sulfanilamide polymorphism was undertaken. We studied 3 known polymorphs of sulfanilamide by 14N NQR. We found at room temperature 2 sets of 3 14N NQR transition frequencies, corresponding to 2 different nitrogen sites in the crystal structure for each of 3 polymorphs. We measured the temperature dependence of all quadrupole frequencies ν+, ν-. In each set, only 1 of the 3 14N NQR frequencies is enough to characterize the polymorph. Spin-lattice relaxation time (T1) measurement is supplemental information. We also measured the transition temperature between polymorphs and estimated the ratio of polymorphs after thermal treatment of sample.

Design and Comparative Evaluation of the Anticonvulsant Profile, Carbonic-Anhydrate Inhibition and Teratogenicity of Novel Carbamate Derivatives of Branched Aliphatic Carboxylic Acids with 4-Aminobenzensulfonamide.

Epilepsy is one of the most common neurological diseases, with between 34 and 76 per 100,000 people developing epilepsy annually. Epilepsy therapy for the past 100+ years is based on the use of antiepileptic drugs (AEDs). Despite the availability of more than twenty old and new AEDs, approximately 30% of patients with epilepsy are not seizure-free with the existing medications. In addition, the clinical use of the existing AEDs is restricted by their side-effects, including the teratogenicity associated with valproic acid that restricts its use in women of child-bearing age. Thus, there is an unmet clinical need to develop new, effective AEDs. In the present study, a novel class of carbamates incorporating phenethyl or branched aliphatic chains with 6-9 carbons in their side-chain, and 4-benzenesulfonamide-carbamate moieties were synthesized and evaluated for their anticonvulsant activity, teratogenicity and carbonic anhydrase (CA) inhibition. Three of the ten newly synthesized carbamates showed anticonvulsant activity in the maximal-electroshock (MES) and 6 Hz tests in rodents. In mice, 3-methyl-2-propylpentyl(4-sulfamoylphenyl)carbamate(1), 3-methyl-pentan-2-yl-(4-sulfamoylphenyl)carbamate (9) and 3-methylpentyl, (4-sulfamoylphenyl)carbamate (10) had ED50 values of 136, 31 and 14 mg/kg (MES) and 74, 53, and 80 mg/kg (6 Hz), respectively. Compound (10) had rat-MES-ED50 = 13 mg/kg and ED50 of 59 mg/kg at the mouse-corneal-kindling test. These potent carbamates (1,9,10) induced neural tube defects only at doses markedly exceeding their anticonvuslnat-ED50 values. None of these compounds were potent inhibitors of CA IV, but inhibited CA isoforms I, II and VII. The anticonvulsant properties of these compounds and particularly compound 10 make them potential candidates for further evaluation and development as new AEDs.