Search Results (19)

Deep eutectic solvents (DESs) are popular green media used for various industrial, pharmaceutical, and biomedical applications. However, the possible compositions of eutectic systems are so numerous that it is impossible to study all of them experimentally. To remedy this limitation, the solubility landscape of selected active pharmaceutical ingredients (APIs) in choline chloride- and betaine-based deep eutectic solvents was explored using theoretical models based on machine learning. The available solubility data for the selected APIs, comprising a total of 8014 data points, were collected for the available neat solvents, binary solvent mixtures, and DESs. This set was augmented with new measurements for the popular sulfa drugs in dry DESs. The descriptors used in the machine learning protocol were obtained from the σ-profiles of the considered molecules computed within the COSMO-RS framework. A combination of six sets of descriptors and 36 regressors were tested. Taking into account both accuracy and generalization, it was concluded that the best regressor is nuSVR regressor-based predictive models trained using the relative intermolecular interactions and a twelve-step averaged simplification of the relative σ-profiles. Full article

The C(sp²)-aryl sulfonate functional group is found in bioactive molecules, but their synthesis can involve extreme temperatures (>190 °C or flash vacuum pyrolysis) and strongly acidic reaction conditions. Inspired by the 1917 Tyrer industrial process for a sulfa dye that involved an aniline N(sp²)-SO₃ intermediate en route to a C(sp²)-SO₃ rearranged product, we investigated tributylsulfoammonium betaine (TBSAB) as a milder N-sulfamation to C-sulfonate relay reagent. Initial investigations of a stepwise route involving TBSAB on selected anilines at room temperature enabled the isolation of N(sp²)-sulfamate. Subsequent thermal rearrangement demonstrated the intermediary of a sulfamate en route to the sulfonate; however, it was low-yielding. Investigation of the N-sulfamate to C--sulfonate mechanism through control experiments with variation at the heteroatom positions and kinetic isotope experiments (KIE^H/D) confirmed the formation of a key N(sp²)-SO₃ intermediate and further confirmed an intermolecular mechanism. Furthermore, compounds without an accessible nitrogen (or oxygen) lone pair did not undergo sulfamation- (or sulfation) -to-sulfonation under these conditions. A one-pot sulfamation and thermal sulfonation reaction was ultimately developed and explored on a range of aniline and heterocyclic scaffolds with high conversions, including N(sp²)-sulfamates (O(sp²)-sulfates) and C(sp²)-sulfonates, in up to 99 and 80% (and 88% for a phenolic example) isolated yield, respectively. Encouragingly, the ability to modulate the ortho-para selectivity of the products obtained was observed under thermal control. A sulfonated analog of the intravenous anesthetic propofol was isolated (88% yield), demonstrating a proof-of-concept modification of a licensed drug alongside a range of nitrogen- and sulfur-containing heterocyclic fragments used in drug discovery. Full article

The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide–sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme. Full article

A new series of 4-((7-methoxyquinolin-4-yl) amino)-N-(substituted) benzenesulfonamide 3(a–s) was synthesized via the reaction of 4-chloro-7-methoxyquinoline 1 with various sulfa drugs. The structural elucidation was verified based on spectroscopic data analysis. All the target compounds were screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and unicellular fungi. The results revealed that compound 3l has the highest effect on most tested bacterial and unicellular fungal strains. The highest effect of compound 3l was observed against E. coli and C. albicans with MIC = 7.812 and 31.125 µg/mL, respectively. Compounds 3c and 3d showed broad-spectrum antimicrobial activity, but the activity was lower than that of 3l. The antibiofilm activity of compound 3l was measured against different pathogenic microbes isolated from the urinary tract. Compound 3l could achieve biofilm extension at its adhesion strength. After adding 10.0 µg/mL of compound 3l, the highest percentage was 94.60% for E. coli, 91.74% for P. aeruginosa, and 98.03% for C. neoformans. Moreover, in the protein leakage assay, the quantity of cellular protein discharged from E. coli was 180.25 µg/mL after treatment with 1.0 mg/mL of compound 3l, which explains the creation of holes in the cell membrane of E. coli and proves compound 3l’s antibacterial and antibiofilm properties. Additionally, in silico ADME prediction analyses of compounds 3c, 3d, and 3l revealed promising results, indicating the presence of drug-like properties. Full article

Antibiotics must be safe and effective for use in both human and veterinary medicine. However, information about the efficacy of different brands of antibiotics commonly used in veterinary practices is lacking in Ethiopia. In this study, we determined the efficacy of three brands of penicillin–streptomycin (Pen&strep, Penstrep, and Pro&strep) by performing antimicrobial susceptibility testing against Staphylococcus aureus isolated from cow milk from dairy farms in the towns of Sebata and Bishoftu, Central Ethiopia. We also assessed the knowledge, attitudes, and practices (KAP) of veterinarians regarding the quality and use of brand antibiotics and the antibiotic utilization practices of dairy farm personnel using a structured questionnaire. Of 43 S. aureus isolated and tested, 33 (77%), 10 (23%), and 1 (2%) were susceptible to brands A, B, and C, respectively. According to the respondents, all of them reported that penstrep is the most prescribed antibiotic in dairy farms (100%), followed by oxytetracycline (78%) and sulfa drugs (52%). All veterinarians perceived that antibiotics imported from Western countries have a higher efficacy than those from Eastern countries, and they preferred brand A to the other brands, witnessing its better clinical outcome. The majority (87%) and a little more than half (53%) of the respondents perceived the overuse of antibiotics in veterinary clinics and dairy farms, respectively. Our study revealed the better efficacy of brand A against S. aureus compared to the other brands. Interestingly, the veterinarians’ perception of and preference toward the use of brand antibiotics agreed with the findings of our antibacterial susceptibility testing. The prudent use of brand A is critically important for sustaining effective treatment, avoiding the risk of antimicrobial resistance, and helping to address animal welfare issues. Full article

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(H₂O+SDZ−H)⁺ and Zn(H₂O+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(OH₂)(SDZ−H)⁺ and Zn(OH₂)(STZ−H)⁺ lie 63 and 26 kJ mol⁻¹ 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. Full article

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a–c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a–c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs. Full article

This paper addresses the prediction of the adsorption behavior as well as the inhibition capacity of non-toxic sulfonamide-based molecules, also called sulfa drugs, on the surface of mild steel. The study of the electronic structure was investigated through quantum chemical calculations using the density functional theory method (DFT) and the direct interaction of inhibitors with the iron (Fe) metal surface was predicted using the multiple probability Monte Carlo simulations (MC). Then, the examination of the solubility and the environmental toxicity was confirmed using a chemical database modeling environment website. It was shown that the presence of substituents containing heteroatoms able to release electrons consequently increased the electron density in the lowest unoccupied and highest occupied molecular orbitals (LUMO and HOMO), which allowed a good interaction between the inhibitors and the steel surface. The high values of E_HOMO imply an ability to donate electrons while the low values of E_LUMO are related to the ability to accept electrons thus allowing good adsorption of the inhibitor molecules on the steel surface. Molecular dynamics simulations revealed that all sulfonamide molecules adsorb flat on the metal surface conforming to the highly protective Fe (1 1 0) surface. The results obtained from the quantum chemistry and molecular dynamics studies are consistent and reveal that the order of effectiveness of the sulfonamide compounds is P7 > P5 > P6 > P1 > P2 > P3 > P4. Full article

During pregnancy, there is a state of immune tolerance that predisposes them to viral infection, causing maternal-fetal vulnerability to the adverse effects of COVID-19. Bacterial coinfections significantly increase the mortality rate for COVID-19. However, it is known that all drugs, including antibiotics, will enter the fetal circulation in a variable degree despite the role of the placenta as a protective barrier and can cause teratogenesis or other malformations depending on the timing of exposure to the drug. Also, it is important to consider the impact of the indiscriminate use of antibiotics during pregnancy can alter both the maternal and fetal-neonatal microbiota, generating future repercussions in both. In the present study, the literature for treating bacterial coinfections in pregnant women with COVID-19 is reviewed. In turn, we present the findings in 50 pregnant women hospitalized diagnosed with SARS-CoV-2 without previous treatment with antibiotics; moreover, a bacteriological culture of sample types was performed. Seven pregnant women had coinfection with Staphylococcus haemolyticus, Staphylococcus epidermidis, Streptococcus agalactiae, Escherichia coli ESBL +, biotype 1 and 2, Acinetobacter jahnsonii, Enterococcus faecium, and Clostridium difficile. When performing the antibiogram, resistance to multiple drugs was found, such as macrolides, aminoglycosides, sulfa, dihydrofolate reductase inhibitors, beta-lactams, etc. The purpose of this study was to generate more scientific evidence on the better use of antibiotics in these patients. Because of this, it is important to perform an antibiogram to prevent abuse of empirical antibiotic treatment with antibiotics in pregnant women diagnosed with SARS-CoV-2. Full article

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system. Full article

To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid 1 reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid 2–6a,b. Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems 10–15, respectively. Ethoxycarbonylamino derivate 5 reacted with some nucleophiles containing the NH₂ group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives 16–20a,b. Compound 4 reacted with the same nucleophiles to give the methylidene amino derivatives 21–24a,b. The fused compound 10 reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems 25–30, respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi. Full article

This paper, reports on the novel and green synthesis procedure for sulfonamides that involved the immobilization of Trametes Versicolor laccase onto the Fe₃O₄–graphene nanocomposite via glutaraldehyde (GA) crosslinking (Lac/Fe₃O₄/GO). Various parameters, mainly, activation time, GA, and laccase concentration were investigated and optimized. The results showed that the optimal contact time was 4 h, GA concentration was 5% while laccase concentration was 5 mg·mL⁻¹, at which a high enzyme activity recovery was achieved (86%). In terms of the stability of immobilized laccase to temperature and storage conditions, the performance of the nanobiocatalyst was found to significantly exceed that of free laccase. The results have indicated that nearly 70% of relative activity for immobilized laccase remained after the incubation period of 2 h at 55 °C, but only 48% of free laccase remained within the same time period. Moreover, the immobilized laccase retained 88% of its initial activity after storage for 20 days. In case of the free laccase, the activity retained within the same time period was 32%. In addition, the nanobiocatalyst possessed better recycling performance as evidenced from the observation that after eight cycles of repeated use, it retained 85% of its original activity. Full article

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S. aureus, showed the highest susceptibility, with minimum inhibitory concentration values from 7.81 µM. The growth of Candida sp. and Trichophyton interdigitale was inhibited at concentrations starting from 1.95 µM. 4-[(2,5-Dihydroxybenzylidene)amino]-N-(pyrimidin-2-yl)-benzenesulfonamide was identified as the most selective Schiff base for these strains with no apparent cytotoxicity and a selectivity index higher than 16. With respect to M. tuberculosis and M. kansasii that were inhibited within the range of 8 to 250 µM, unsubstituted 4-[(2-hydroxy-benzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide meets the selectivity requirement. In general, dihalogenation of the salicylic moiety improved the antibacterial and antifungal activity but also increased the cytotoxicity, especially with an increasing atomic mass. Some derivatives offer more advantageous properties than the parent sulfadiazine, thus constituting promising hits for further antimicrobial drug development. Full article

Sulfonamides (SAs) represent a significant category of pharmaceutical compounds due to their effective antimicrobial characteristics. SAs were the first antibiotics to be used in clinical medicine to treat a majority of diseases, since the 1900s. In the dairy farming industry, sulfa drugs are administered to prevent infection, in several countries. This increases the possibility that residual drugs could pass through milk consumption even at low levels. These traces of SAs will be detected and quantified in milk. Therefore, microextraction techniques must be developed to quantify antibiotic residues, taking into consideration the terms of Green Analytical Chemistry as well. Full article

Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug–containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models. Full article