Sulphonamide Drugs Research Articles

Selective graphene-based electrochemical sensing platform for enhanced sulfamethoxazole assay

Antibiotics are currently considered as a major source of pollution. Sulfamethoxazole (SFX), an antibacterial sulphonamide drug, commonly prescribed and employed in a variety of bacterial infections, was reported to have a multitude of adverse health reactions, therefore its quantification in pharmaceutical industry, medicine and environment is of great interest. This study reports a novel graphene-based electrochemical sensing platform for enhanced SFX detection. Graphene material was prepared by electrochemical exfoliation at 19 V applied bias, in 0.05 M boric acid/0.05 M sodium chloride mixed solution. The performances of the graphene-modified glassy carbon electrode (GR/GCE) were evaluated in terms of selectivity, sensitivity, accuracy, and reproducibility employing cyclic voltammetry, differential pulse voltammetry, and amperometry. Under optimized conditions, at pH 5, the developed sensor shows a remarkable enhancement of the sensing abilities compared to the bare electrode, with a linear response in the 0.009 – 28.8 µM SFX concentration range, and a low limit of detection: 0.00272 µM. Furthermore, the analytical applicability of the modified electrode in real sample analysis was performed on two commercially available pharmaceutical formulations. The results of the study demonstrate that the developed sensing platform is able to achieve high selectivity and sensitivity for SFX detection, thus providing a reliable and cost-effective solution for SFX assay.

A-272 Challenges in Designing an Antibiotic Gene Resistance Panel for Clinical Use

Abstract Background We faced 3 major challenges in our journey of designing a custom panel for antibiotic resistance genes (ABR). Challenge 1# Fast, robust, and affordable antimicrobial resistance testing (ABR) In general, qPCR-based methods are efficient, reliable, and fast with high specificity and sensitivity, and with the test results available within 2–3 h. We offer urinary tract infection identification by qPCR and wanted to supplement this test with detection of antibiotic resistance genes. we narrowed our choice of method to be qPCR based, Applied Biosystems™ OpenArray™ technology on the Applied Biosystems™ QuantStudio™ 12K Flex Real-Time PCR System. Challenge2# Genes to be tested. Antibiotic resistance occurs via various mechanism. Based on the literature review, we included the following gene in our custom panel 1. Aminoglycosides: aac(6′)-Ib-cr6, aac(6′)-Ib-cr, aac(6′)-Ib-cr4 2. Tetracycline: tet(M), tet(B) 3. Sulfonamides: sul1, sul2 4. Macrolide-lincosamide-streptogramin B-ketolides-oxazolidinones: erm C, erm A, erm B 5. Quinolone/(fluoroquinolones): qnrS , qnrA, aac(6′)-Ib-cr6, aac(6′)-Ib-cr, aac(6′)-Ib-cr4 6. Glycopeptides: VanA, VanB 7. Beta-lactam Class A: SHV, KPC, CTX-M 8. Beta-lactam Class B: NDM, VIM, IMP 9. Beta-lactam Class C: CMY, DHA, FOX, KPC 10. Beta-lactam Class D: OXA1, OXA-23, OXA- 48, 11. Methicillin resistance: mecA. Results Validation of the ABR panel Accuracy: 50 isolates were ordered from CDC AR isolate bank and were used to test the accuracy. The accuracy was detected to be 98% concordant. Sensitivity: The assay was sensitive to detect all urinary pathogens upto 10^3 CFU/mL. Precision: the inter and intra reproducibility was shown to be 99% concordant Specific: when tested against the CDC controls, the assays were 100% specific Challenge 3# Genotype—Phenotype correlation and prevalence of antibiotic resistance genes in USA. We compared 100 consecutive clinical specimens (urine) for genotype -phenotype co-relation. Data from the current qPCR panel and Microscan instrument was compared. It was observed for the pathogens that were phenotypically resistant to certain antibiotics, the corresponding gene association was not found in (2–50%) of antibiotic groups. This can be explained due to the limited number of genes in each drug class. Resistance to some antibiotics such as nitrofurantoin drug (100% missed) and sulphonamide drug resistance (50% missed) is induced by point mutations, which are not captured in open array genotyping qPCR assay. To overcome this gap between genotype and phenotype correlation and to understand the prevalence of antibiotic resistance genes in USA, we initiated a new project. We aim to test for 300–400 clinical samples which known resistance phenotypes and check for antibiotic resistance gene in a new expanded panel. We were successful in designing the new panel to include 88 genes (vs 30 genes in the old panel). Conclusion The current assay was approved by the CLIA authorities for clinical testing. In general, qPCR-based methods are efficient, reliable, and fast with high specificity and sensitivity, and with the test results available within 2–3 h.

QSAR Studies on Some Sulfonamides as Antidiabetic Agents

The need for antidiabetic agents is growing day by day in pharmaceutical industry to find novel, potent and more specialized class of medicine. To address the need we have evaluated a set of sulphonamide drugs for their potential to fight against diabetes. In the present study antidiabetic activity of 47 sulfonamide derivatives have been modeled using topological descriptors. The activity in terms of pKi have been modeled using descriptors calculated from Dragon software. The best model having R2 value 0.9897 have been reported after deleting two outliers. The model was tested using Cross validated method. The R2cv value for the reported five-parametric model comes out to be 0.9896. The model has also been tested for collinearity or defect of Chance. It has been established that the model is free from any defect. The author suggests the testing of these compound for in vivo studies to specify the other pharmacological significance and therapeutic potential for future use.

A negative partial volume of methanol in aqueous solutions: How plausible is it? Some comments on “Intermolecular interactions between methanol and some sulphonamide drugs in aqueous medium using thermodynamics approach” by indra Bahadur et al. [J. Mol. Liq. 283 (2019) 451–461

The authors of the above paper came recently to the inference that the apparent (down to infinite dilution) molar volumes of methanol in water and aqueous sulphonamides are negative in sign and unusually large in magnitude. In this regard, two main points relating to the given “phenomenon” were considered here: how plausible is it and what experimental “features” did the authors apply to achieve such a result? Based on the recalculated authors’ data and reliable literature data of interest, it is concluded here on the scientific absurdity of results reported in the paper being commented. The main reasons for this could be the sloppy performing experimental procedures as well as the incorrect using well-known thermodynamic relations by the authors (Bahadur et al.).

Sulfonamide drugs: structure, antibacterial property, toxicity, and biophysical interactions.

Sulfonamide (or sulphonamide) functional group chemistry (SN) forms the basis of several groups of drug. In vivo sulfonamides exhibit a range of pharmacological activities, such as anti-carbonic anhydrase and anti-t dihydropteroate synthetase allowing them to play a role in treating a diverse range of disease states such as diuresis, hypoglycemia, thyroiditis, inflammation, and glaucoma. Sulfamethazine (SMZ) is a commonly used sulphonamide drug in veterinary medicine that acts as an antibacterial compound to treat livestock diseases such as gastrointestinal and respiratory tract infections. Sulfadiazine (SDZ) is another frequently employed sulphonamide drug that is used in combination with the anti-malarial drug pyrimethamine to treat toxoplasmosis in warm-blooded animals. This study explores the research findings and the work behaviours of SN (SMZ and SDZ) drugs. The areas covered include SN drug structure, SN drug antibacterial activity, SN drug toxicity, and SN environmental toxicity.

Determination of Solubility of 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic Acid and its Sodium Salt in Acetonitrile and Voltammetric Investigation of Sulphonamide Drugs in Different Solvents in Their Absence and Presence

Sulphonamide drugs (sulphamethazine, sulphamerazine, sulphadiazine, sulphathiazole) were studied in a wide potential window (between 2 and − 2 V) in acetonitrile, dimethyl sulphoxide and in 50–50 v/v% binary mixtures of acetonitrile and water. The voltammograms of the outlined compounds were very similar both in the anodic and cathodic part in each non-aqueous solvents except for sulphathiazole. These sulphonamide drugs were also investigated in presence of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and its sodium salt and the voltammograms changed due to an acid–base reaction. HEPES and its sodium salt could be investigated in acetonitrile only in their saturation concentration as they were slightly soluble in this solvent. In a separate experiment their solubilities were determined at 298 K in acetonitrile with the co-solvent calibration method using water as co-solvent. Complementary fluorescence studies in dimethyl sulphoxide did not show the presence of any interaction between sulphonamide drugs and HEPES as well as its sodium salt.

Paediatrics in Theresienstadt ghetto.

The main objective of this study is to describe the most common childhood diseases occurring in the Theresienstadt ghetto during the Second World War as well as applied anti-epidemic measures. A partial objective is to describe medical and nursing care of sick child prisoners. The data was obtained by the method of synthesis of primary and secondary data with the highest importance after adequate external source criticism using selected monographs, memoirs, survivor diaries, Orders of the day by the Council of the Elders and Reports of the Jewish self-government of the Theresienstadt ghetto from 1941 to 1945, the Archives of the Jewish Museum in Prague, the Ghetto Museum, the Museum of the History of Polish Jews in Warsaw, Post Bellum online electronic collection of oral historical interviews, and witness accounts. The validity of the presented conclusions is ensured by comparing data from several sources. The most common infections in Theresienstadt children were enteritis, scarlet fever, infectious jaundice, measles, mumps, rubella, varicella, black cough, pneumonia, otitis media, and typhoid fever. Most of these infections had entirely atypical symptomatology or complications. Children were hospitalized in children's hospitals, in children's rooms of hospitals for adults and infirmaries in children's homes. Albeit diagnostic methods had a high standard, options of treatment were very limited. The most common treatments included bed rest, diet and cold compress. Occasionally, chemotherapeutic agents (e.g. a sulphonamide drug Prontosil) and Aspirin were available. The anti-epidemic measures in the ghetto focused on hygiene, enhancing children's immunity, vaccination and pest control.

Comments on “Intermolecular interactions between methanol and some sulphonamide drugs in aqueous medium using thermodynamics approach”

The negative values of the apparent molal volumes of methanol reported by Bahadur and coworkers are incorrect, and not consistent with the experimental densities reported in the paper. Moreover, the authors' calculated negative values for the apparent molal volume of methanol in water are inconsistent with published values taken from the chemical literature.

Intermolecular interactions between methanol and some sulphonamide drugs in aqueous medium using thermodynamics approach

Interactions between methanol and some sulphonamide drugs namely sulphamethizole, sulphabenzamide, sulphaquinoxaline and sulphachloropyridazine were investigated. Physical parameters such as densities (ρ), sound velocities (u) and viscosities (ƞ) were measured, and the effects of temperature and concentration on aqueous phase interactions were deduced. Other physical quantities like apparent molar volumes, Vφ, apparent molar adiabatic compressibilities, kφ, viscosity B-coefficients and temperature coefficient (dB/dT) were derived from measured data. Corresponding partial molar quantities were determined by employing Redlich-Mayer type equation. Sulphamethizole and sulphabenzamide are regarded as structure breakers based on positive values of dB/dT, while sulphaquinoxaline and sulphachloropyridazine are considered to be structure makers due to negative values of dB/dT.

Anti-Helicobacter pylori activity of ethoxzolamide

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10−9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.

Characterization of multiple life stages of two Australian Fasciola hepatica isolates in sheep

Information on the susceptibility status of Fasciola hepatica isolates is lacking in the literature, even for those isolates considered to be laboratory reference strains. Four controlled efficacy studies were conducted on two Fasciola hepatica isolates from Australia, viz. ‘Oberon’ and ‘Sunny Corner’ with treatment at either 2, 6 or 10 weeks post-infection (wpi) as defined in each study. Fluke burdens and examination of livers occurred at necropsy in weeks 12 (Study 1) or 13 (Studies 2, 3 and 4) post-infection. The triclabendazole (TCBZ) resistance status of the Oberon isolate was confirmed in 6 and 10-week old F. hepatica, utilizing the drug alone (Fasinex; 71.5% and 31.1%, respectively) and in combination with oxfendazole (Flukazole C; 79.9% and 0%, respectively). The susceptibility of this isolate to albendazole, as well as salicylanilide and sulphonamide drugs was confirmed. The Sunny Corner isolate was confirmed as susceptible to TCBZ (>99% all stages) and closantel (>90% at ≥6 wpi).

Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates

A series of monothiocarbamates (MTCs) was investigated for the inhibition of the β-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite Malassezia globosa, MgCA. These MTCs incorporate various scaffolds, among which aliphatic amine with 1–4 carbons atom in their molecule, morpholine, piperazine, as well as phenethylamine and benzylamine derivatives. All the reported MTCs displayed a better efficacy in inhibiting MgCA compared to the clinically used sulphonamide drug acetazolamide (KI of 74 μM), with KIs spanning between 1.85 and 18.9 μM. The homology model of the enzyme previously reported by us was used to rationalize the results by docking some of these MTCs within the fungal CA active site. This study might be useful to enrich the knowledge of the MgCA inhibition profile, eliciting novel ideas pertaining the design of modulators with potential efficacy in combatting dandruff or other fungal infections.

The NMR Study and Antimicrobial Activity of Some Schiff Bases Derived From Sulphonamide Drug

Some Schiff base compounds derived from sulfonamide drug were synthesized by reaction of 4-aminobenzenesulfonamide with aromatic aldehydes (2-hydroxy-1-naphthaldehyde, 3,4-dihydroxybenzaldehyde and 2-hydroxy benzaldehyde) in good yields. Characterization of synthesized compound was carried by elemental analysis, IR, 1H,13C, HSQC and HMBC- NMR spectroscopy. The synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Streptococcus sp., Bacillus subtillus, Escherichia coli and Klebsiella pneumonia. Additionally, the compounds were tested for antifungicidal activity against Candida krusei, Candida tropicalis, Aspergillus fumigates and Aspergillus niger.

Synthesis, antimicrobial activity and modelling studies of some new metal complexes of Schiff base derived from sulphonamide drug in vitro

Palladium(II) and cobalt(II) complexes of Schiff base derived from 4-aminobenzene sulfonamide (Sulfonamide drug) were prepared by convenient method. Reaction of sulfonamide with 2-hydroxy-1-naphthaldehyde gave the Schiff base compound 1 in good yield. Treatment of compound 1 with CoCl 2 .6H 2 O and PdCl 2 yielded new metal complexes 2 and 3 , respectively. The synthesized compounds were screened for their antibacterial activity against Escherichia coli , Bacillus cereus , Salmonella spp. and Staphylococcus aureus . Additionally, the compounds were tested for antifungal activity against Aspergillus niger and Candida albicans . Some compounds exhibited good antibacterial and antifungal activity. Molecular modeling studies were performed and showed hydrogen binding and hydrophobic interactions.

'Smashed by the National Health'? A Closer Look at the Demise of the Pioneer Health Centre, Peckham.

The Pioneer Health Centre, based in South London before and after the Second World War, remains a source of interest for advocates of a positive approach to health promotion in contrast with the treatment of those already ill. Its closure in 1950 for lack of funds has been blamed on the then recently established National Health Service, but this article argues that such an explanation is over-simplified and ignores a number of other factors. The Centre had struggled financially during the 1930s and tried to gain support from the Medical Research Council. The Council appeared interested in the Centre before the war, but was less sympathetic in the 1940s. Around the time of its closure and afterwards, the Centre was also involved in negotiations with London County Council; these failed because the Centre’s directors would not accept the changes which the Council would have needed to make. Unpublished documents reveal that the Centre’s directors were uncompromising and that their approach to the situation antagonised their colleagues. Changes in medical science also worked against the Centre. The success of sulphonamide drugs appeared to render preventive medicine less significant, while the development of statistical techniques cast doubt on the Centre’s experimental methods. The Centre was at the heart of the nascent organic farming movement, which opposed the rapid growth of chemical cultivation. But what might be termed ‘chemical triumphalism’ was on the march in both medicine and agriculture, and the Centre was out of tune with the mood of the times.

Late Acute Myopia Syndrome Induced by Combination of Sulfonamide Drugs

We present a case of late acute myopia syndrome following discontinuation of treatment with a combination of sulphonamide drugs. To the best of our knowledge, this is the first reported case with such a presentation, and suggests that the pathophysiological basis for the acute myopia syndrome is a rapid decrease in serum carbonic anhydrase inhibitors levels which may lead to a rebound increase in the production of aqueous humor and accumulation of suprachoroidal fluid. It is further postulated that there may be a cumulative effect of sulphonamide drug use on carbonic anhydrase activity in the ciliary body epithelium of susceptible individuals.

Cutaneous manifestations of Nocardia brasiliensis infection in Taiwan during 2002–2012—clinical studies and molecular typing of pathogen by gyrB and 16S gene sequencing

To observe the clinicopathologic and resistance profiles of the Nocardia brasiliensis causing cutaneous nocardiosis in Taiwan, 12 N. brasiliensis isolates were prospectively collected from patients with cutaneous nocardiosis in a hospital during 2002–2012. Clinicopathologic data were obtained, and isolates were identified by biochemical methods and 16S rRNA sequencing. Susceptibilities to 14 antimicrobial compounds were tested. Isolates were further genotyped by sequencing of 16S rRNA, secA1, hsp65, and gyrB genes. The nodulopustular pyoderma associated with sporotrichoid spreading was the most common skin presentations caused by N. brasiliensis. All of the isolates were susceptible to amikacin, gentamicin, tobramycin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole and resistant to kanamycin, erythromycin, and oxacillin, while susceptibilities to imipenem, vancomycin, penicillin-G, tetracycline, clindamycin, and ciprofloxacin varied among the 12 isolates. GyrB genotyping delineated the 12 isolates into 2 major groups, which was coincident with different single nucleotide substitutions at position 160 (G versus T) of 16S rRNA, different levels of imipenem minimum inhibition concentration (4–32 versus 0.25–0.75 mg/L), and prevalence of lymphadenitis (66.7 versus 16.7%). We have noted that tiny pustular lesions can be the first sign of cutaneous nocardiosis, which we believe has not been previously emphasized. No resistance to trimethoprim and sulfamethoxazole was found; therefore, sulphonamide drugs remain effective for treatment of cutaneous nocardiosis in Taiwan.

Efficacy of Different Concentrations of Aloe chabaudii Leaf Gel as a Substitute for a Sulfonamide for the Control of Avian Coccidiosis

The objective of this study was to investigate the effectiveness of Aloe chabaudii schonland juice as a potential substitute of sulphonamide drugs and to measure its effects when administered at different concentrations in the control of avian coccidiosis. 30 cobb and 500 broiler chickens were used for the experiment. The broilers were randomised into six groups of five birds each and the groups were assigned to six treatments in a Complete Randomised Design (CRD). Four of the groups were given any one of the following treatments, different concentrations of Aloe (weight/volume: 10%, 20% and 30%) and a sulphonamide. There was a control group which was not given a treatment and one cohort group which was neither infected nor treated. At two weeks of age, 25 of the birds were infected with coccidia via drinking water using infected chicken fecal matter, while the remaining five birds were left uninfected. Infection proceeded for 1 week and after the infection period, fecal oocysts were counted from each individual bird using the McMaster technique. Treatments started one day after the infection and continued for one week after 20 gram samples of fecal matter were taken from each bird per treatment and oocysts were counted. After oocyst counting, all birds were slaughtered and lesion scoring was done on the intestines using the Johnson and Reid technique. Data was analysed for oocysts count in different treatments, fecal egg count reduction, relative risk of coccidiosis and the effectiveness of Aloe concentrations as a substitute for a commercial sulphonamide. The results showed that the concentrations of Aloe used in the experiment were not effective as compared to the sulphonamide in controlling coccidiosis as the fecal egg reduction was below 90% for all concentrations. The relative risk of coccidiosis infection in the farm was found to be 100%, meaning that coccidiosis is a disease of economic importance at the farm. However, there was a reduction in the fecal oocyst count with increase in Aloe juice concentration to control coccidiosis, though this could not be compared to sulphonamide (ESB3) which was more effective (p 0.05). This study has shown that there is potential for use of Aloe chabaudii leaf gel as a chemotherapeutic though much research is needed to determine absolute concentrations which will make it comparable to commercially available drugs in terms of efficacy.

The war against bacteria: how were sulphonamide drugs used by Britain during World War II?

Penicillin is often considered one of the greatest discoveries of 20th century medicine. However, the revolution in therapeutics brought about by sulphonamides also had a profound effect on British medicine,...

Novel LTCC-potentiometric microfluidic device for biparametric analysis of organic compounds carrying plastic antibodies as ionophores: Application to sulfamethoxazole and trimethoprim

Monitoring organic environmental contaminants is of crucial importance to ensure public health. This requires simple, portable and robust devices to carry out on-site analysis. For this purpose, a low-temperature co-fired ceramics (LTCC) microfluidic potentiometric device (LTCC/μPOT) was developed for the first time for an organic compound: sulfamethoxazole (SMX). Sensory materials relied on newly designed plastic antibodies. Sol–gel, self-assembling monolayer and molecular-imprinting techniques were merged for this purpose. Silica beads were amine-modified and linked to SMX via glutaraldehyde modification. Condensation polymerization was conducted around SMX to fill the vacant spaces. SMX was removed after, leaving behind imprinted sites of complementary shape. The obtained particles were used as ionophores in plasticized PVC membranes. The most suitable membrane composition was selected in steady-state assays. Its suitability to flow analysis was verified in flow-injection studies with regular tubular electrodes. The LTCC/μPOT device integrated a bidimensional mixer, an embedded reference electrode based on Ag/AgCl and an Ag-based contact screen-printed under a micromachined cavity of 600 μm depth. The sensing membranes were deposited over this contact and acted as indicating electrodes. Under optimum conditions, the SMX sensor displayed slopes of about −58.7 mV/decade in a range from 12.7 to 250 μg/mL, providing a detection limit of 3.85 μg/mL and a sampling throughput of 36 samples/h with a reagent consumption of 3.3 mL per sample. The system was adjusted later to multiple analyte detection by including a second potentiometric cell on the LTCC/μPOT device. No additional reference electrode was required. This concept was applied to Trimethoprim (TMP), always administered concomitantly with sulphonamide drugs, and tested in fish-farming waters. The biparametric microanalyzer displayed Nernstian behaviour, with average slopes −54.7 (SMX) and +57.8 (TMP) mV/decade. To demonstrate the microanalyzer capabilities for real applications, it was successfully applied to single and simultaneous determination of SMX and TMP in aquaculture waters.