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A 2‐year‐old cat was referred for suspected generalised seizure activity and reclusive behaviour, with a history of non‐resolving facial abscess. Magnetic resonance imaging (MRI) revealed a contrast enhancing lesion occupying the left calvarium and adjacent peripheral tissues. The intracranial lesion was causing significant mass effect, with oedema and transtentorial herniation. Nocardia nova was isolated from the lesion and identified by DNA sequencing. Treatment consisted of debridement via craniotomy and ventral bulla osteotomy, and combination antibiotic therapy with clarithromycin, amoxycillin and trimethoprim‐sulfonamide (sulfadoxine parenterally, then sulfadiazine orally). After several weeks of antibiotic therapy, the cat developed weakness, bicavitary effusion, myxoedema, non‐regenerative anaemia and azotaemia. Total thyroxine (TT4) was below the detectable limit and canine thyroid stimulating hormone (cTSH) assay was markedly elevated at 7.53 ng/mL (reference interval 0.15–0.3 ng/mL). Discontinuation of sulfonamides and administration of levothyroxine resulted in resolution of clinical signs. The cat was subsequently able to discontinue levothyroxine, with recovery of euthyroid state. To the authors' knowledge, this is the first report of clinical hypothyroidism in a cat treated with sulfonamide antibiotics and may influence antimicrobial selection and monitoring during therapy. This report also described the management of an atypical presentation of nocardiosis with intracranial extension. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a leading cause of global mortality, with dyslipidemia being a significant modifiable risk factor. Dyslipidemia refers to all abnormalities in blood lipid levels. It plays a fundamental role in the development and progression of atherosclerosis. The reduction of low‐density lipoprotein (LDL) cholesterol has been shown to decrease cardiovascular risk. Cholesteryl ester transfer protein (CETP) plays a role in LDL metabolism, and its inhibition results in lower LDL levels. This study synthesizes and evaluates novel benzene sulfonamide derivatives as CETP inhibitors. Twenty compounds were synthesized and tested for their inhibitory activity using an in vitro bioassay. The results revealed that para‐methylated derivatives exhibited higher inhibitory activity compared to meta‐methylated derivatives, where compound 6n has an IC50 of 24.4 µM. Furthermore, electron withdrawing groups such as chlorine and nitro substitutions on the sulfanamido‐phenyl rings demonstrated superior inhibitory effects compared to electron donating groups. Positional isomerism of the substitutions also influenced inhibitory activity, with para substitutions being more effective. Nitro‐substituted compounds showed greater inhibition than chlorine‐substituted compounds, where compound 6t has an IC50 of 18.3 µM. Overall, this study provides valuable insights into the SAR of CETP inhibitors and identifies promising compounds for further investigation as potential therapeutics for CVD. [ABSTRACT FROM AUTHOR]

Piperazine, a nitrogen‐containing heterocyclic compound, has potential in medical chemistry due to its versatile structure and ease of modification. Therefore, researchers have designed novel piperazine derivatives with various biological activities, including antiviral, antibacterial, and antifungal properties. In this study, a new series of 2‐(4‐((5‐bromo‐2‐methoxyphenyl)sulfonyl) piperazine‐1‐yl) acetamide derivatives (7a‐l) were synthesized and their structures were identified using 1H‐NMR, 13C‐NMR, and HRMS spectroscopic methods. The in vitro antimicrobial activity of these compounds was tested against four bacterial strains and two fungi strains. Some of the sulfonyl piperazine derivatives (7d, 7e, 7f, 7j, 7k, and 7l) exhibited relatively good antimicrobial and antifungal activities compared to standard drugs. Further analysis using computational docking confirmed strong binding interactions, aligning with our results. Our compounds exhibited improved potency compared to existing standard treatments. [ABSTRACT FROM AUTHOR]

ABSTRACT The title compound, C17H25N3O3S2, hereafter 1, has been prepared and fully characterized by FTIR, 1H NMR and 13C NMR. Its crystal structure was determined by single‐crystal X‐ray diffraction. The crystal packing is stabilized by weak CH···O and CH···π interactions. The CLP‐Pixel method was used to quantify the energetically significant molecular dimers. The intermolecular contacts were identified and quantified using Hirshfeld surfaces (HS) and the corresponding fingerprint plots. The main contributions to the HS of 1 come from HH, OH/HO and CH/HC contacts, which cover about 93% of the total HS surface. The enrichment ratios showed that the favorable contacts accountable for the crystal packing are consistent with their contributions to the HS. Interaction region indicator (IRI) analysis was used to visualize the location and type of intermolecular contacts, allowing identify the CH···O contacts as van der Waals interactions. To visualize the 3D topology of interactions in the crystal structure, interaction energy values were used to construct energy framework diagrams, which showed that the dispersion energy dominates over other interaction energies, as expected for crystal packing governed by weak interactions. Finally, a combination of MEP surface, QTAIM and NCIplot analysis energetically confirmed the existence of CH···O and O···O dichalcogen interactions. [ABSTRACT FROM AUTHOR]

Glycolysis is a highly conserved biochemical process that involves the sequential conversion of glucose to pyruvate and the generation of adenosine triphosphate (ATP), generating energy for cellular functions. This is carried out by several enzymes that play an important role in glucose metabolism. The sulfonamide group of drugs is commonly used as an antibiotic that inhibits the bacterial folic acid production pathway, although its effects on glycolytic enzymes are unclear. Since altered glycolytic enzyme expression is linked to a variety of metabolic disorders as well as cancer, the quest for new ligands against glycolytic enzymes is never over. We revealed that different sulfonamide derivatives interact with glycolytic enzymes with varying binding affinities. Among the selected sulfonamides, sulfisoxazole and sulfamethazine had greater binding scores to certain glycolytic enzymes than others. In silico point mutation analysis predicts that sulfisoxazole and sulfamethazine interact with certain glycolytic enzymes in a residue‐independent manner. This research generates a repository of the 2D interactions of sulfonamide derivatives with glycolytic enzymes, binding energies, impacts of induced point mutations on the local environment, and changes in protein structural flexibility. In the future, sulfisoxazole and sulfamethazine may be repurposed as specific glycolytic enzyme inhibitors to combat a variety of glycolysis‐related metabolic disorders. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. α‐Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible α‐glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (1–16). Findings suggested that all compounds have better α‐glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1‐deoxynojirimycin (334.90 ± 1.10 μM), with IC50 values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound 13, a trichloro phenyl substituted compound, with IC50 value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound 13 established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative condition is expected to affect 152 million in 2050. The current study comprises the evaluation of thiazole based thiadiazole bearing sulfonamide derivatives to treat Alzheimer's disease. A series of compounds (1‐15) were synthesized and were studied for their anti‐Alzheimer's potential. Their IC50 values lie in the range between (19.20±0.20 nM–2.50±0.20 nM) for AChE and (19.80±0.20 nM–3.30±0.50 nM) for AChE. Among all of them, analog 2, 7, 9, and 15 were reported to possess significant activity. Among all the members of series, compound 15 having IC50=2.50±0.20 nM and 3.30±0.50 nM for AChE and BuChE, respectively, emerged as the most promising candidate due to the presence of two electronegative fluorine (F) atoms. The small and highly electronegative fluorine atoms have the ability to block the enzyme's activity by forming strong hydrogen bonds with the amino acids of the target enzymes, thereby inhibiting their function. The efficacy of these novel compounds was studied in comparison to the standard drug donepezil having IC50=5.80±0.30 nM for AChE and IC50=6.30±0.81 nM BuChE. For further assessment of inhibition potential and mode of inhibition, molecular docking study of all the potent compounds was carried out. Further, the structural identity of the synthesized compounds was confirmed using various spectroscopic techniques, including 1H‐NMR, 13C‐NMR, and High‐Resolution Electron Impact (HREI) Mass spectrometry, which provided detailed information about their molecular structure. ADME analysis of all the synthesized compounds confirmed their potential as drugs, indicating favorable pharmacokinetic properties and a promising drug profile. [ABSTRACT FROM AUTHOR]

An efficient one-pot approach was proposed for the synthesis of novel sulfonyl-1H-1,2,3-triazolo-1H-imidazole-2-sulfonamides. The newly synthesized derivatives were screened for in vitro antibacterial inhibition potency against gram-positive strains. Among the tested compounds, N-({1-[(4-chlorophenyl)sulfonyl]-1H-1,2,3-triazol-4-yl}methyl)-1-methyl-1H-imidazole-2-sulfonamide and N-({1-[(4-cyanophenyl)sulfonyl]-1H-1,2,3-triazol-4-yl}methyl)-1-methyl-1H-imidazole-2-sulfonamide had a minimum inhibitory concentration (MIC) of 3.12 μg/mL against B. subtilis, which is two times higher than the normal streptomycin (6.25 μg/mL). It also had a MIC value of 6.25 μg/mL against S. aureus that was the same as the positive control. Also the antibiofilm profiles for the potent compounds showed that the active derivatives were not only very good at killing bacteria, but they were also very good at stopping the growth of B. subtilis biofilm. [ABSTRACT FROM AUTHOR]

Sulfur(VI)‐based functional groups are popular scaffolds in a wide variety of research fields including synthetic and medicinal chemistry, as well as chemical biology. The growing interest in sulfur(VI)‐containing molecules has motivated the scientific community to explore new methods to synthesize and modify them. Here, photocatalysis plays a key role granting access to new types of reactivity under mild reaction conditions. In this Perspective, we present a selection of works reported in the last six years focused on the photocatalytic assembly and reactivity of sulfones, sulfonamides, and sulfoximines. We addressed the key synthetic intermediates for each transformation, while discussing limitations and strength points of the protocols. Future directions of the field are finally presented. [ABSTRACT FROM AUTHOR]

New optically active arylsulfonamides, including carane-containing streptocide analogs, were synthesized by the reaction of carane amino alcohols with tosyl- and N-acetylsulfanilyl chlorides. Sulfonamide, which was prepared based on (–)-4β-amino-3α-hydroxy-cis-carane, was studied by X-ray diffraction. The synthesized sulfonamides and the starting amino alcohols were evaluated for antimicrobial activity. [ABSTRACT FROM AUTHOR]

Research into novel anti-Helicobacter pylori agents represents an important approach for the identification of new treatments for chronic gastritis and peptic ulcers, which are associated with a high risk of developing gastric carcinoma. In this respect, two series of azobenzenesulfonamides were designed, synthesized, and tested against a large panel of human and bacterial CAs to evaluate their inhibitory activity. In addition, computational studies of the novel primary benzenesulfonamides (4a–j) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus H. pylori of the two series was also studied. The best-in-class compounds were found to be 4c and 4e among the primary azobenzenesulfonamides and 5c and 5f belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti-H. pylori activity, with MIC values of 4–8 μg/mL and MBCs between 4 and 16 μg/mL. Moreover, the evaluation of their toxicity on a G. mellonella larva in vivo model indicated a safe profile for 4c,e and 5c,f. The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti-H. pylori agents. [ABSTRACT FROM AUTHOR]

This study developed a highly sensitive microbiological method utilizing a novel microtiter plate to screen 10 sulfonamides in chicken muscles, eggs, and prawns. This plate was fabricated from agar incorporating trimethoprim and spread with Bacillus megaterium. After residue detection by bioassay, the same test solutions were analyzed by LC-MS/MS for accurate identification and quantification. It also proved eco-friendly compared to using other quantitative methods. The residual drugs were extracted with McIlvaine buffer and purified using an Oasis® MCX cartridge. A triethylamine/methanol/water (0.5:75:24.5, v/v/v) mixture was used as the eluate. The obtained LOD values of the bioassay ranged from 5 to 25 µg kg−1 allowing the detection of the target drugs at the MRLs established in Japan. Adhering to ISO/IEC 17025 standards, the performance of the bioassay was evaluated. Based on the inhibition zone size in bioassay results, quality control yielded a Z score within ±2, indicating reasonable control over the screening process. Proficiency testing of a chicken muscle sample spiked with sulfadimidine demonstrated the inhibition zone detection of the bioassay and quantified value alignment of LC-MS/MS with reference values. In a surveillance study of 91 samples, sulfamethoxazole was detected in one prawn sample. [ABSTRACT FROM AUTHOR]

Sulfonamides are auspicious chemosensors which are capable to bind with ionic species through various ways like complexation, charge transfer, proton transfer etc. and produce a detection signal in the form of an optical change either in visible or UV-light and for electronic as well as fluorimetric spectra. Sulfonamides have gained much attention of analytical chemists these days as these are inexpensive, robust, green in nature and some what sensitive and selective to many anionic and cationic species. Due to their promising versatility in sensing properties, these are under great consideration in forensic, environmental, analytical and biochemistry laboratories. This review narrates how sulfonamides are being used to optically sense ionic species. HIGHLIGHTS: Optical sensors are of great importance these days because of their optical detection properties rather using Hi-tech techniques. Optical sensors are economical, robust, selective, sensitive and green in nature. The color change, shifts in electronic spectra or alterations in fluorescence pattern may be attributed by interaction between species to be sensed and Sulfonamides by different mechanism i.e. electron transfer, fluorescence energy transfer, charge transfer, hydrogen bonding, etc. LOD data is a proof of their prodigious efficiency of Sulfonamides as optical sensors. [ABSTRACT FROM AUTHOR]

A novel series of benzenesulfonamide substituted spirothiazolidinone derivatives (3a–j) were synthesized, characterized and evaluated for their antiviral activity. The spirocyclic compounds were prepared by the condensation of 4-(aminosulfonyl)-2-methoxybenzohydrazide, appropriate cyclic ketones and 2-mercaptopropionic acid in a one-pot reaction. The structures of the new compounds were established by IR, 1H NMR, 13C NMR (APT), and elemental analysis. The new compounds were evaluated in vitro antiviral activity against influenza A/H1N1, A/H3N2 and B viruses, as well as herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and yellow fever virus (YFV). Two derivatives bearing propyl (3d) and tert-butyl (3e) substituents at position 8 of the spiro ring exhibited activity against influenza A/H1N1 virus with EC50 values in the range of 35–45 µM and no cytotoxicity at 100 μM, the highest concentration tested. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis of bicyclo[1.1.1]pentane (BCP)‐containing sulfonamides via a transition metal‐free process of a three‐component reaction among BCP‐containing N‐tosyl hydrazones, 1,4‐diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and amines. Different from existing methods to synthesize BCP‐containing sulfonamides, our method avoids the usage of sulfonyl halides, which could be challenging due to chemical instabilities. We have also demonstrated that this methodology is suitable for library synthesis of such sulfonamides. As a result, we can expect future application in drug discovery. [ABSTRACT FROM AUTHOR]

Electrochemical or photochemical single-electron oxidation of bench-stable substrates can generate radical cations that offer unique reactivities as intermediates in various bond-formation processes. Such intermediates can potentially take part in both radical and ionic bond formation; however, the mechanisms involved are complicated and not fully understood. Herein, we report electrochemical radical cation aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes.

The title compound, [Re(C17H22N3O2S)(CO)3] is a net neutral fac-Re(I)(CO)3 complex of the 4-methylbiphenyl sulfonamide derivatized diethylenetriamine ligand. The NNN-donor monoanionic ligand coordinates with the Re core in tridentate fashion, establishing an inner coordination sphere resulting in a net neutral complex. The complex possesses pseudo-octahedral geometry where one face of the octahedron is occupied by three carbonyl ligands and the other faces are occupied by one sp2 nitrogen atom of the sulfonamide group and two sp3 nitrogen atoms of the dien backbone. The Re—Nsp2 bond distance, 2.173 (4) Å, is shorter than the Re—Nsp3 bond distances, 2.217 (5) and 2.228 (6) Å, and is similar to the range reported for typical Re—Nsp2 bond lengths (2.14 to 2.18 Å).

Abstract In this study, we synthesized new series of 5-oxo-2-phenyl-4-(arylsulfamoyl)sulphenyl) hydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate hybrids 4a-f with the goal of overcoming sulfonamide resistance and identifying novel therapeutic candidates by chemical changes. The chemical structures of the synthesized hybrids were established over the spectroscopic tools. The frontier molecular orbitals configuration and energetic possessions of the synthesized compounds were discovered utilizing DFT/B3LYP/6-311++ G** procedure. The 3D plots of both HOMO and LUMO showed comparable configuration of both HOMO and LUMO led to close values of their energies. Amongst the prepared analogues, the sulfonamide hybrids 4a-f, hybrid 4a presented potent inhibitory towards S. typhimurium with (IZD = 15 mm, MIC = 19.24 µg/mL) and significant inhibition with (IZD = 19 mm, MIC = 11.31 µg/mL) against E.coli in contrast to sulfonamide (Sulfamethoxazole) reference Whereas, hybrid 4d demonstrated potent inhibition with (IZD = 16 mm, MIC = 19.24 µg/mL) against S. typhimurium with enhanced inhibition against E. Coli, Additionally, the generated sulfonamide analogues’' molecular docking was estimated over (PDB: 3TZF and 6CLV) proteins. Analogue 4e had the highest documented binding score as soon as linked to the other analogues. The docking consequences were fitting and addressed with the antibacterial valuation.

Acetazolamide 1 is a carbonic anhydrase inhibitor used in the medical treatment of glaucoma, epileptic seizure, idiopathic intracranial hypertension, altitude sickness, etc. The synthesis of acetazolamide from the corresponding thiol derivative 4 requires oxidation and converting it to the sulfonyl chloride intermediate 5. This research aimed to enhance the safety, environmental conditions, and efficiency of the oxidation process by substituting chlorine gas for sodium hypochlorite (commercial bleach). The use of chlorine gas in place of conventional oxidation methods offered significant benefits, including the synthesis of several novel compounds with a high level of purity, specifically designated as 6a-6f. These novel compounds were produced through the reaction of synthesized key sulfonyl chloride 5 with various amines, hydrazones, and bis-amine precursors, leading to the creation of new sulfonamide derivatives. A thorough investigation was conducted to determine the antibacterial activity (ABA) and antioxidant activity (AOA) of the newly synthesized compounds. The results indicated that the ABA impact of the prefabricated bis-products (7a and 7b) was significantly higher than that of the standard mono-product (6a). This suggests that the bis-products possess enhanced antibacterial properties compared to their mono-product counterparts. Moreover, the hydrazine-based products synthesized (8a-8g) demonstrated remarkable efficacy against both Gram-positive and Gram-negative bacteria. These products, particularly compound 9g, showed superior antibacterial effects when compared to commonly used antibiotics such as ciprofloxacin and tetracycline. This highlights the potential of these new compounds as effective antibacterial agents. In terms of antioxidant activity, a comparison with ascorbic acid revealed that compounds 9c, 9a, 9b, 9e, and 8d exhibited superior AOA. This indicates that these compounds have a strong potential to act as antioxidants, which can be beneficial in various applications where oxidative stress is a concern. In summary, the substitution of chlorine gas for sodium hypochlorite in the oxidation process not only improved safety and environmental conditions but also led to the efficient synthesis of highly pure novel compounds. These compounds displayed significant ABA and AOA, suggesting their potential as valuable agents in medical and industrial applications. The enhanced properties of the bis-products and hydrazine-based compounds, in particular, underscore the importance of this research in developing new, effective chemical entities. Future research will focus on further optimizing these compounds for clinical use, evaluating their pharmacokinetics and toxicity profiles, and exploring their applications in other therapeutic areas such as anticancer and antiviral treatments. [ABSTRACT FROM AUTHOR]

Cinchona alkaloid-derived sulfonamides and ester dimers containing chiral hyperbranched polymers have been successfully synthesized and applied as catalysts in asymmetric reactions. Several hyperbranched polymers derived from cinchona alkaloids, incorporating sulfonamides and esters, were synthesized through Mizoroki--Heck coupling polymerization. These polymers were subsequently applied in enantioselective Michael addition reactions. As the prepared polymers are not soluble in frequently used organic solvents, they act as efficient catalysts in the enantioselective reaction of β-ketoesters to nitroolefins, achieving up to 99% enantioselectivity with good yields. The insoluble property allows them to better satisfy "green chemistry" requirements and be used several times without losing the enantioselectivity. [ABSTRACT FROM AUTHOR]

A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors. [ABSTRACT FROM AUTHOR]

Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, 10–13, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds 10–13 were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds 10–13. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is E. Biological results revealed that all the screened compounds 10–13 might serve as selective COX-1 inhibitors. They showed IC50 values ranging from 0.71 μM to 4.82 μM against COX-1 and IC50 values ranging from 9.26 μM to 15.24 μM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC50 values ranging from 0.11 μM to 0.37 μM, surpassing the standard aspirin with an IC50 value of 0.49 μM. Additionally, they inhibited the platelet aggregation induced by collagen with IC50 values ranging from 0.12 μM to 1.03 μM, demonstrating superior efficacy compared to aspirin, which has an IC50 value of 0.51 μM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of E-forms with respect to Z-forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors. [ABSTRACT FROM AUTHOR]

Objective: In 2016, Spodoptera frugiperda invaded Africa and caused serious economic damage. To protect crops from this dangerous pest, it was necessary to use all plant protection methods, like biological and chemical control. Producing powerful pesticides for the efficient management of this pest was the interest of many scientists around the world. Methods: A large number of chemical compounds were synthesized and tested for their toxicological activity against this new invading pest. The synthesized pyrazole derivatives are the subject of the first study on the harmful effects they cause, followed by structural relationships. Following the stated protocols, five pyrazole derivatives were synthesized as pure active ingredients, and their efficacy as potential insecticides against S. frugiperda was tested. Results and Discussion: The toxicity data exhibited that compound (VIb), with LC50 of 8.81 and 16.16 ppm, was more toxic than other synthesized insecticidal agents against the 2nd and 4th larval instars, respectively. The other checked compounds showed weak to strong insecticidal activity in the final category; the biological effects of the synthesized insecticidal agents on S. frugiperda under laboratory conditions were also investigated. These findings were validated via molecular docking investigations of the titled compounds against the gamma-aminobutyric acid receptor (GABA), which had PDB ID: 4COF.The results showed a strong interaction of (IVb) and (VIb) with the target 4COF protein with a high negative docking score. [ABSTRACT FROM AUTHOR]

Chikungunya virus infection has become a global health concern because of its high rates of morbidity and mortality in patients with preexisting conditions. Inflammation and arthritis are the major symptoms of CHIKV that persist even after clearance of CHIKV. To develop an antiviral that can reduce infection and manage inflammation independent of the CHIKV infection, ibuprofen (IBU) conjugates with sulfonamide and thiosemicarbazide were synthesized. The conjugates, IBU-SULFA, IBU-ISS and IBU-IBT significantly inhibited CHIKV infection in vitro with a selectivity index (CC50/IC50) of > 11.9, > 25.1 and > 21, respectively. The reduction in infection was attributed to the interference of the conjugates in the early stages of CHIKV life cycle. With no acute oral toxicity, these compounds significantly reduced inflammation and arthritis in rats. Unlike IBU, the conjugates were not ulcerogenic. In conclusion, the conjugation imparted anti-CHIKV properties while retaining the anti-inflammatory properties of IBU. These findings can encourage further validation and research to develop an antiviral for CHIKV to manage both infection and arthritis. [ABSTRACT FROM AUTHOR]

Sulfonamide compounds with functional group -SO2NH- show a wide range of biological activities and medicinal properties. The synthesis of sulfonamides has been of interest to medicinal chemists for a long time. In this article, the selective acylation of sulfanilamide with acetic anhydride was carried out using some catalysts with Lewis acid properties. In this research, the one-pot selective method of N-acylation of -SO2NH2 group in sulfanilamide molecule using stannous oxide nanoparticles as an efficient recyclable catalyst has been used. In this method, THF was replaced with expensive toxic amine solvents. The acylated product was identified by FTIR, 1HNMR, 13CNMR and MASS spectra. The best results with 85% efficiency, 95% selectivity were obtained using stannous oxide nanoparticles as catalyst (0.5 g) in tetrahydrofuran as solvent, at 60°C in 60 minutes. The catalyst was recycled three times and maintained its efficiency. Using this method is completely green and has economic and environmental benefits. [ABSTRACT FROM AUTHOR]

In this study, we synthesized new series of 5-oxo-2-phenyl-4-(arylsulfamoyl)sulphenyl) hydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate hybrids 4a-f with the goal of overcoming sulfonamide resistance and identifying novel therapeutic candidates by chemical changes. The chemical structures of the synthesized hybrids were established over the spectroscopic tools. The frontier molecular orbitals configuration and energetic possessions of the synthesized compounds were discovered utilizing DFT/B3LYP/6-311++ G** procedure. The 3D plots of both HOMO and LUMO showed comparable configuration of both HOMO and LUMO led to close values of their energies. Amongst the prepared analogues, the sulfonamide hybrids 4a-f, hybrid 4a presented potent inhibitory towards S. typhimurium with (IZD = 15 mm, MIC = 19.24 µg/mL) and significant inhibition with (IZD = 19 mm, MIC = 11.31 µg/mL) against E.coli in contrast to sulfonamide (Sulfamethoxazole) reference Whereas, hybrid 4d demonstrated potent inhibition with (IZD = 16 mm, MIC = 19.24 µg/mL) against S. typhimurium with enhanced inhibition against E. Coli, Additionally, the generated sulfonamide analogues'' molecular docking was estimated over (PDB: 3TZF and 6CLV) proteins. Analogue 4e had the highest documented binding score as soon as linked to the other analogues. The docking consequences were fitting and addressed with the antibacterial valuation. [ABSTRACT FROM AUTHOR]

In 2014, the World Health Organization called drug resistance to antibiotics a "major global threat". Therefore, the ever‐increasing human need for new antibiotics with greater effectiveness and fewer side effects is a necessity. Meanwhile, sulfonamides are among the most widely used antibiotics in the world. In this review, attention has been paid to the key points raised in various papers in the field of electrosynthesis of these compounds, considering their positive and negative aspects, including interaction as much as possible with the principles of green chemistry and the absence of environmental risks, low cost and the versatility and scalability of the method used along with acceptable efficiency. In the following, we will discuss research focused on the synthesis of sulfonamide derivatives based on the oxidation or reduction of various compounds which take place on the working electrode surface. [ABSTRACT FROM AUTHOR]

Klassische Schutzgruppenchemie erfordert unweigerlich einen Entschützungsschritt, um die ursprünglich blockierte Funktionalität vor weiteren Umwandlungen wiederherzustellen. Da dieser Aspekt der Schutzgruppenmanipulation zwangsläufig die Anzahl der Schritte jeder Synthesesequenz erhöht, bieten Methoden, die eine gleichzeitige Entschützung und Funktionalisierung ermöglichen („entschützende Funktionalisierung", im Gegensatz zur Entschützung mit anschließender Funktionalisierung), attraktive Vorteile, um die Effizienz zu steigern und synthetische Routen zu verkürzen. In diesem Bericht präsentieren wir eine Methode zur entschützenden Funktionalisierung der neu eingeführten Nms‐Amide, die auf einer Analyse mittels Dichtefunktionaltheorie (DFT) basiert und die inhärente Nms‐Reaktivität ausnutzt. Mechanistische Studien erklären außerdem warum andere häufig verwendete Schutzgruppen nicht die gleichen Reaktivitätsmuster aufweisen. Die Anwendbarkeit dieses Ansatzes wurde anhand zahlreicher Substrate demonstriert und schließlich verwendet, um Arzneimittelderivate effizienter und mit verkürzten Synthesewegen herzustellen. [ABSTRACT FROM AUTHOR]

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, represents the most prevalent malignancy in women, with over 2 million new diagnoses annually throughout the world. Chemotherapy remains a mainstay in breast cancer therapy, but drug resistance and severe side effects are the major causes for treatment failure. Sulfonamides could act on diverse proteins, enzymes, and receptors and demonstrated promising anti-breast cancer potential. In particular, sulfonamide hybrids have the potential to overcome drug resistance and reduce the side effects since hybrid molecules could act on dual/multiple targets simultaneously. This review focuses on the anti-breast cancer activity, structure-activity relationships, and mechanisms of action of sulfonamide-five-membered heterocycle hybrids, including sulfonamide-azole hybrids, sulfonamide-7-azaindole/indole/oxindole/indoline hybrids, sulfonamide-furan hybrids, and sulfonamide-thiophene hybrids, covering articles published from 2020 to present, to open new avenues for the exploration of novel more effective and multitargeted candidates. [ABSTRACT FROM AUTHOR]

The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH‐triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer‐based and organic–inorganic nanomaterial constructs. Although the GSH‐triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple‐targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH‐triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH‐triggered prodrugs in the future. By assessing the pros and cons of current GSH‐triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH‐triggered prodrugs. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title compound, 2C31H28N2O4S·C2H6O, contains a parent molecule and a half molecule of ethanol solvent. The main compound stabilizes its molecular conformation by forming a ring with an R12(7) motif with the ethanol solvent molecule. In the crystal, molecules are connected by C—H...O and O—H...O hydrogen bonds, forming a three-dimensional network. In addition, C—H...π interactions also strengthen the molecular packing.

Background and objective: Sulfonamides are a type of antibiotic that are used to treat several infections caused by microorganisms. Sulfonamides are bacteriostatic, meaning they prevent bacterial growth. This study aimed to produce compounds with better antimicrobial activity. Methods: By condensation reaction, Schiff bases were synthesized from sulfonamides (sulfamethoxazole, sulfapyridine, sulfathiazole, sulfadiazine and sulfisoxazole) and vanillin to enhance antimicrobial activity of synthesized compounds. The agar dilution method was used to measuring the minimum inhibition concentration (MIC) of synthesized compounds. Results: The synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR and tested for the antibacterial activity against gram positive bacteria (Staphylococcus aureus), gram negative bacteria (Escherichia coli) and antifungal activity against (Candida albicans). Ciprofloxacin and Fluconazole used as standard drugs for bacteria and fungi. Conclusion: The Schiff base was synthesized, characterized, and exhibited enhanced antimicrobial and antifungal activities.

Introduction: The determination of biotransformation products is an essential part of the preclinical trial of original medicines. These studies have not been conducted before for the new drug 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. Identification and synthesis of metabolite substances are necessary for subsequent tests of bioavailability, linearity of pharmacokinetics, accumulation, distribution and excretion. Materials and methods: The study was carried out on Wistar rats and rabbits of the Soviet Chinchilla breed. The substance of the drug was administered to animals intraperitoneally. The collection of animal blood samples was performed before administration and 1 h, 2 h, 4 h, 24 h after administration into K3EDTA-tubes. A part of each sample was centrifuged to separate the plasma. Rat urine samples were taken before administration and at intervals of 0-2 h, 2-4 h, 4-6 h, 6-24 h after administration of the drug. The HPLC-MS/MS method was used to identify metabolites in biological fluids. The assumed biotransformation products were synthesized after preliminary analysis. The structure of the obtained substances was confirmed by NMR spectroscopy and high-resolution mass spectrometry. Then, a comparison was carried out with the compounds identified in biological fluids by retention time, ratios of chromatographic peak areas at the main MRM-transitions using HPLC-MS/MS. Results and discussion: A metabolite formed by addition an oxygen atom to a drug molecule, as well as an acylated metabolite were detected during the analysis of plasma and blood samples. A compound with an increased molecular weight of 1 dalton compared to the drug substance was also present in a rat urine. N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide, 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid, which could potentially be obtained during biotransformation, as well as N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide were synthesized. Repeated HPLC-MS/MS tests confirmed the correctness of the initial hypothesis. It was found that a sulfonic acid derivative is formed in urine as a result of decomposition of N-hydroxymetabolite during sample collection. Conclusion: The studied drug is metabolized by formation of two metabolites: N-hydroxy-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide and N-acetyl-5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonamide. N-hydroxymetabolite is able to decompose in biological fluids samples with formation of 5-[5-(trifluoromethyl)-1,2-oxazole-3-yl]-furan-2-sulfonic acid.

Abstract The present study investigates the potential of a new compound containing sulfonamide and 4(3H)-quinazolinone to inhibit the hCA-IIX enzyme using in silico methods. Density functional theory-based calculations of electronic properties have been addressed through the analysis of frontier molecular orbitals, molecule electrostatic potential, and IR and UV–vis spectroscopy data. A molecular electrostatic potential analysis predicts that the target protein will be most inhibited by the sulfonamide groups since it has the highest potential spots for electrophile and nucleophile attack. The investigated compound exhibited good ADMET properties and satisfied the Lipinski rule of drug likeness. The hCA-IIX protein binding affinity with the proposed compound was determined by molecular docking analysis, which revealed a stable conformation with more negative binding energy (−12.19 kcal/mol) than the standard AZA drug (−7.36 kcal/mol). Moreover, a molecular dynamics study confirmed the docking results through trajectory analysis. The RMSD and RMSF both showed convergence and no significant fluctuations during the simulation time, which revealed a stable interaction within the active domain of the target protein. According to these findings, the proposed compound has a good pharmacological nature and could potentially be an efficient drug against hCAIX enzymes.

Abstract Background Bioaugmentation has the potential to enhance the ability of ecological technology to treat sulfonamide-containing wastewater, but the low viability of the exogenous degraders limits their practical application. Understanding the mechanism is important to enhance and optimize performance of the bioaugmentation, which requires a multifaceted analysis of the microbial communities. Here, DNA-stable isotope probing (DNA-SIP) and metagenomic analysis were conducted to decipher the bioaugmentation mechanisms in stabilization pond sediment microcosms inoculated with sulfamethoxazole (SMX)-degrading bacteria (Pseudomonas sp. M2 or Paenarthrobacter sp. R1). Results The bioaugmentation with both strains M2 and R1, especially strain R1, significantly improved the biodegradation rate of SMX, and its biodegradation capacity was sustainable within a certain cycle (subjected to three repeated SMX additions). The removal strategy using exogenous degrading bacteria also significantly abated the accumulation and transmission risk of antibiotic resistance genes (ARGs). Strain M2 inoculation significantly lowered bacterial diversity and altered the sediment bacterial community, while strain R1 inoculation had a slight effect on the bacterial community and was closely associated with indigenous microorganisms. Paenarthrobacter was identified as the primary SMX-assimilating bacteria in both bioaugmentation systems based on DNA-SIP analysis. Combining genomic information with pure culture evidence, strain R1 enhanced SMX removal by directly participating in SMX degradation, while strain M2 did it by both participating in SMX degradation and stimulating SMX-degrading activity of indigenous microorganisms (Paenarthrobacter) in the community. Conclusions Our findings demonstrate that bioaugmentation using SMX-degrading bacteria was a feasible strategy for SMX clean-up in terms of the degradation efficiency of SMX, the risk of ARG transmission, as well as the impact on the bacterial community, and the advantage of bioaugmentation with Paenarthrobacter sp. R1 was also highlighted . Video Abstract

الملخص: أهداف البحث: كان الهدف من هذه الدراسة هو تصميم وإتاحة السلفوناميدات المضادة للسرطان عن طريق اقتران الأمينات وكلوريد الدانسيل مع البدائل الإستراتيجية. وباستخدام تقنيات الرنين المغناطيسي النووي ومطياف الكتلة، تم تشخيص الهياكل المركبة. أيضا، تم استخدام تحليل الالتحام الجزيئي لمعرفة مدى ارتباط السلفوناميدات المصنوعة حديثا بـ 5-أسيتاميدو-1،3،4-ثياديازول-2-سلفوناميد، وهو هدف دوائي محتمل. استلزم هذا التقييم مقارنة ارتباطاتها الملزمة بتلك الموجودة في عقار الأسيتازولاميد المعروف. طريقة البحث: تم تصنيع السلفوناميدات عن طريق اقتران الأمينات وكلوريد الدانسيل في ظل ظروف مواتية للغاية. أدرجت السلفوناميدات المصممة بدائل ذات موقع استراتيجي لنقل خصائص بيولوجية متنوعة. تم التحقق من صحة الهياكل المركبة باستخدام الرنين المغناطيسي النووي وأطياف الكتلة. تم إجراء تحليل الالتحام الجزيئي لتقييم الارتباطات الملزمة للسلفوناميدات المركبة مع الهدف الدوائي المحتمل 5-أسيتاميدو-1،3،4-ثياديازول-2-سلفوناميد. النتائج: تم بنجاح تصنيع السلفوناميدات من خلال اقتران الأمينات وكلوريد الدانسيل. أكد التحقق من صحة الهياكل المركبة باستخدام الرنين المغناطيسي النووي وأطياف الكتلة هوياتها الكيميائية. كشف تحليل الالتحام الجزيئي أن السلفوناميدات المُصنّعة أظهرت ارتباطات ربط تتراوح من -6.8 إلى -8.2 كيلو كالوري / مول مع هدف الدواء المحتمل 5-أسيتاميدو-1،3،4-ثياديازول-2-سلفوناميد. الأهم من ذلك، أن جميع المشتقات أظهرت ارتباطات ربط متفوقة مقارنة بالأسيتازولاميد (-5.25 سعرة حرارية/مول). الاستنتاجات: أتاح اقتران الأمينات وكلوريد الدانسيل التوليف الفعال والمباشر للسلفوناميدات. إن التصميم الاستراتيجي للسلفوناميدات مع بدائل محددة سيوفر خصائص بيولوجية متنوعة، بما في ذلك إمكانية النشاط المضاد للسرطان. إن توضيح المركبات المحضرة باستخدام الرنين المغناطيسي النووي وأطياف الكتلة أكد بنيتها. أظهر تحليل الالتحام الجزيئي أن السلفوناميدات المصنعة أظهرت ارتباطات مواتية مع هدف الدواء المحتمل 5-أسيتاميدو-1،3،4-ثياديازول-2-سلفوناميد. والجدير بالذكر أن جميع المشتقات أظهرت ارتباطات ربط أعلى تتراوح من -6.8 إلى -8.2 كيلو كالوري/مول من عقار الأسيتازولاميد الموصى به (-5.25 كيلو كالوري/مول)، مما يشير إلى إمكاناتها كنظائر فعالة للغاية لمزيد من التحقق من الصحة في علاج السرطان. Abstract: Objectives: The goal of this study was to design and enable development of anticancer sulfonamides by coupling amines and dansyl chloride with strategically selected substituents. The synthesized structures were characterized by NMR and mass spectrometry. In addition, molecular docking analysis was used to determine the binding ability of sulfonamides toward 1AZM, a possible drug target, as compared with that of the well-known drug acetazolamide. Methods: Sulfonamides were synthesized by coupling amines and dansyl chloride under highly favorable conditions. The designed sulfonamides incorporated strategically positioned substituents to impart diverse biological properties. The synthesized structures were validated with NMR and mass spectra. Molecular docking analysis was performed to evaluate the binding affinities of the synthesized sulfonamides with the potential drug target 1AZM. Results: The synthesis of sulfonamides through the coupling of amines and dansyl chloride was successfully achieved. The validation of the synthesized structures with NMR and mass spectra confirmed their chemical identities. Molecular docking analysis revealed that the synthesized sulfonamides displayed binding affinities ranging from −6.8 to −8.2 kcal/mol toward the potential drug target 1AZM. Importantly, all derivatives exhibited superior binding affinities to acetazolamide (−5.25 kcal/mol). Conclusions: The coupling of amines and dansyl chloride enabled efficient, straightforward sulfonamide synthesis. The strategic design of sulfonamides with specific substituents endows diverse biological properties, including potential anti-cancer activity. The elucidation of the synthesized compounds with NMR and mass spectra confirmed their structures. Molecular docking analysis demonstrated that the synthesized sulfonamides exhibited favorable binding affinities toward the potential drug target 1AZM. Notably, all derivatives displayed higher binding affinities, ranging from −6.8 to −8.2 kcal/mol, than the recommended drug acetazolamide (−5.25 kcal/mol), thus suggesting their potential as highly effective analogues for further validation in cancer therapy.

ABSTRACT: Sulfonamides (S) are old bacteriostatic antibiotics which are widely prescribed in combination with trimethoprim (TMP) for the treatment of various diseases in food-producing animals such as poultry. Nowadays, the 1:5 dose ratio of TMP/S used in broilers is a direct transposition of the ratio determined in Human decades ago for TMP/sulfamethoxazole (SMX), aiming to obtain a supposed synergistic plasma concentration ratio of 1:19. However, major pharmacokinetics (PK) differences exist according to the sulfonamide used in the combination. Here, we generated new PK data in broilers after a cross-over design with IV and the oral administration of 2 major sulfonamides, sulfadiazine (SDZ) and SMX, in combination with TMP, and analyzed the data via a population pharmacokinetic (popPK) modeling approach. Results showed that TMP has a greater plasma to tissue distribution than both sulfonamides with a higher volume of distribution (0.51 L/kg for SDZ, 0.62 L/kg for SMX and 3.14 L/kg for TMP). SMX has the highest elimination half-life (2.83 h) followed by SDZ and TMP (2.01 h and 1.49 h, respectively). The oral bioavailability of the 3 molecules was approximately 100%. Bodyweight could explain some of the inter-individual variability in the volume of distribution of SDZ and SMX and the clearance of SDZ and TMP, as heavier broilers have higher typical values. Monte Carlo simulations of a large virtual broiler population (n = 1,000) showed that the targeted plasma ratio of TMP:S of 1:19 was rarely or never reached at the individual level for both combinations at the marketed doses and greatly varies over time and between individuals, questioning the relevance of the 1:5 dose ratio for current formulations of TMP/S.

The inhibitory effects of veralipride, a benzamide‐class antipsychotic acting as dopamine D2 receptors antagonist incorporates a primary sulfonamide moiety and was investigated for its interactions with carbonic anhydrase (CA) isoforms. In vitro profiling using the stopped‐flow technique revealed that veralipride exhibited potent inhibitory activity across all tested hCA isoforms, with exception of hCA III. Comparative analysis with standard inhibitors, acetazolamide (AAZ), and sulpiride, provided insights for understanding the relative efficacy of veralipride as CA inhibitor. The study reports the X‐ray crystal structure analysis of the veralipride adduct with three human (h) isoforms, hCA I, II, and CA XII mimic, allowing the understanding of the molecular interactions rationalizing its inhibitory effects against each isoform. These findings contribute to our understanding of veralipride pharmacological properties and for the design of structural analogs endowed with polypharmacological properties. [ABSTRACT FROM AUTHOR]

Cancer, which proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors, is one of the most fatal diseases. Cancer management meets multiple obstacles, and resistance to current therapeutic approaches is the major one. Pyridines/quinolines and sulfonamides can exert the anticancer potential through different mechanisms, and many current available anticancer chemotherapeutics own a pyridine/quinoline or sulfonamide moiety, revealing that pyridine/quinoline and sulfonamide motifs are useful pharmacophores for the discovery of novel anticancer agents. Notably, incorporation of pyridine/quinoline and sulfonamide pharmacophores into one molecule is a promising strategy to overcome drug resistance, improve the activity and reduce the toxicity since pyridine/quinoline-sulfonamide hybrids could simultaneously act on dual/multiple targets in cancer cells. This review outlines the current scenario of pyridine/quinoline-sulfonamide hybrids with the anticancer potential, covering articles published from 2020 onwards, to pave the way for the development of novel more effective and multitargeted anticancer candidates. [ABSTRACT FROM AUTHOR]

A series of twenty one sulfonamide tethered 1,4-disubstituted 1,2,3-triazoles was synthesized in good yields through a facile expeditious click synthetic protocol involving Cu(I) mediated cyclization between terminal alkynes containing ester linkage and 4-azidobenzenesulfonamide. All the synthesized triazoles were characterized using FTIR,1H NMR,13C NMR and HRMS techniques. Synthesized compounds were also evaluated for in vitro antibacterial activity against two Gram positive bacteria (Staphylococcus aureus, Bacillus subtilis) and two Gram negative bacteria (Klebsiella pneumoniae, Escherichia coli) by serial dilution method. In the series, compound 6 l, 3-(1-(4-sulfamoylphenyl)-1H-1,2,3-triazol-4-yl)propyl 4-bromobenzoate with Minimum Inhibitory Concentration (MIC) 0.0134 µmol/mL exhibited appreciable antibacterial activity against all bacterial strains comparable with standard drug Ciprofloxacin (MIC 0.0189 µmol/mL). Further, molecular docking study was also performed to gain insight for binding interactions with dihydropteroate synthase enzyme. [ABSTRACT FROM AUTHOR]

Photocatalytic technology, as an environmentally friendly technology, has a great application promise in the treatment of environmental pollutants caused by residual pharmaceuticals emissions. The Z‐scheme heterojunction of g‐C3N4/g‐C3N4/Pr6O11 (Pr/CN) was successfully prepared by employing melamine, urea, and praseodymium nitrate as co‐precursors. The structure composition and photoelectrochemical properties were characterized by XRD, XPS, EDS, SEM, FETEM, UV–Vis, EIS, photocurrent, and PL analyses. The optimized 5wt%Pr/CN heterojunction degrade 98% of SCP, 85% of SMM, and 87% of SDM, respectively. Taking SCP as an example, the degradation rate is 8 and 11.2 times higher than that of the g‐C3N4/g‐C3N4 homojunction and g‐C3N4, respectively. The remarkable photocatalytic efficiency of Pr/CN heterojunction could be ascribed to enhanced visible light absorption and enhanced migration and separation of photogenerated charge carriers. Furthermore, the degradation products and degradation pathways of SCP and SMM were established by HPLC‐MS/MS analysis. In addition, the toxicity of the intermediate was evaluated with quantitative structure–activity relationship (QSAR) prediction and the biocompatibility of sulfonamide‐degrading solution over the Pr/CN photocatalyst was verified by the growth of wheat seeds. [ABSTRACT FROM AUTHOR]

Objective: Currently, microbial infections are a global threat to human health, and there is an urgent need to develop new and effective antibacterial drugs to treat microbial infections. The main purpose of this article is to study the inhibitory effect of sulfonamide compounds containing 1,2,3-triazole rings on bacteria and fungi, in order to seek new antibacterial drugs. Methods: Several sulfonamide compounds with 1,2,3-triazole rings were prepared and their inhibitory effects on seven common human pathogenic bacteria (E. coli, P. aeruginosa, S. typhimurium, S. aureus, and B. subtili, as s well as the fungi C. albicans, and A. niger) were evaluated. And through MOE and Gaussian software, the new molecular docking simulation and molecular quantification calculation of the synthesized compound were carried out to explain the relationship between the antibacterial effect of the compound and its molecular configuration. Results: The results showed that compounds (VIb), (VId), (VIe), (VIf), (VIi), and (VIj) had good antibacterial activity. Among them, (VIe) and (VIf) had similar inhibitory activity against Candida albicans as the positive control drug fluconazole, and (VI) f also had a certain inhibitory effect on Escherichia coli. Discussion: Through antibacterial experiments, we found that the antibacterial effects of (VIe) and (VIf) were the best among the synthesized compounds. Through molecular docking simulation and molecular quantification calculations, we found that compounds (VIe) and (VI) f had a better docking effect with enzymes and the highest molecular energy. They had higher reaction activity and were easy to interact with microbial enzymes, thus exerting antibacterial effects. At the same time, we found that the introduction of amide bonds containing electron donating groups on the benzene ring in triazole sulfonamide significantly enhances the antibacterial activity of the compound. Therefore, we believe that when the electron cloud density on the 1,2,3-triazole ring increases, the antibacterial effect of the compound will be enhanced. Conclusions: 1,2,3-triazole sulfonamides containing amide bonds can serve as potential antibacterial agents. [ABSTRACT FROM AUTHOR]

A series of novel pyrazole-dicarboxamides were synthesized from pyrazole-3,4-dicarboxylic acid chloride and various primary and secondary sulfonamides. The structures of the new compounds were confirmed by FT-IR, ¹H-NMR, 13C-NMR, and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.024-0.496 µM for hCA I and 0.006-5.441µM for hCA II. Compounds 7a and 7i showed nanomolar level of inhibition of hCA II, and these compounds exhibited high selectivity for this isoenzyme. Molecular docking studies were performed between the most active compounds 7a, 7b, 7i, and the reference inhibitor AAZ and the hCAI and hCAII to investigate the binding mechanisms between the compounds and the isozymes. These compounds showed better interactions than the AAZ. ADMET and drug-likeness analyses for the compounds have shown that the compounds can be used pharmacologically in living organisms. [ABSTRACT FROM AUTHOR]

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The asymmetric unit of the title compound, 2C31H28N2O4S⋅C2H6O, contains a parent molecule and a half molecule of ethanol solvent. The main compound stabilizes its molecular conformation by forming a ring with an R1²(7) motif with the ethanol solvent molecule. In the crystal, molecules are connected by C--H⋯O and O--H⋯O hydrogen bonds, forming a three-dimensional network. In addition, C--H⋯π interactions also strengthen the molecular packing. [ABSTRACT FROM AUTHOR]

The present study investigates the potential of a new compound containing sulfonamide and 4(3H)-quinazolinone to inhibit the hCA-IIX enzyme using in silico methods. Density functional theory-based calculations of electronic properties have been addressed through the analysis of frontier molecular orbitals, molecule electrostatic potential, and IR and UV–vis spectroscopy data. A molecular electrostatic potential analysis predicts that the target protein will be most inhibited by the sulfonamide groups since it has the highest potential spots for electrophile and nucleophile attack. The investigated compound exhibited good ADMET properties and satisfied the Lipinski rule of drug likeness. The hCA-IIX protein binding affinity with the proposed compound was determined by molecular docking analysis, which revealed a stable conformation with more negative binding energy (−12.19 kcal/mol) than the standard AZA drug (−7.36 kcal/mol). Moreover, a molecular dynamics study confirmed the docking results through trajectory analysis. The RMSD and RMSF both showed convergence and no significant fluctuations during the simulation time, which revealed a stable interaction within the active domain of the target protein. According to these findings, the proposed compound has a good pharmacological nature and could potentially be an efficient drug against hCAIX enzymes. [ABSTRACT FROM AUTHOR]

Antibiotics from sulfonamide, fluoroquinolone, and diaminopyrimidine classes are widely used in human and veterinary medicine, and their combined occurrence in the aquatic environment is increasing around the world. In parallel, the understanding of how mixtures of these compounds affect non‐target species from tropical freshwaters is scarce. Thus, this work aimed to study the long‐term reproductive, recovery, and swimming effects of mixtures of 12 antibiotics from three different classes (up to 10 μg L−1) added to freshwater (FWM) and synthetic wastewater (SWM) matrices on freshwater worm Allonais inaequalis. Results revealed that at the reproduction level, the exposure to antibiotics in the SWM matrix does not cause a significant toxic effect on species after 10 days. On the other hand, exposures to initial dose mixtures (10 μg L−1 each) in FWM caused a significant reduction of offspring by 19.2%. In addition, recovery bioassays (10 days in an antibiotic‐free environment) suggested that A. inaequalis has reduced offspring production due to previous exposure to antibiotic mixtures in both matrices. Furthermore, despite slight variation in swimming speed over treatments, no significant differences were pointed out. Regarding antibiotics in the water matrices after 10‐day exposures, the highest concentrations were up to 2.7, 7.8, and 4.2 μg L−1 for antibiotics from sulfonamide, fluoroquinolone, and diaminopyrimidine classes, respectively. These findings suggest that a species positioned between primary producers and secondary consumers may experience late reproductive damage even in an antibiotic‐free zone, after previous 10‐day exposure to antibiotic mixtures. Practitioner Points: A mixture of sulfonamide, fluoroquinolone, and diaminopyrimidine antibiotics in freshwater affects the offspring production of A. inaequalis after 10 days.After the 10‐day antibiotic exposure, the reproduction of A. inaequalis remains affected in an antibiotic‐free environment over the recovery period.The swimming speed of the worms does not change after 10 days of exposure to the antibiotic mixture.The concentration of dissolved solids can limit the natural degradation of sulfonamide, fluoroquinolone, and diaminopyrimidine antibiotics in the aquatic environment. [ABSTRACT FROM AUTHOR]

The discovery of non-toxic compounds with herbicidal activity remains a significant challenge in agricultural weed management practices. In this study, we conducted a comparative analysis of sulfonamide derivatives, namely sulfadiazine, sulfamerazine, and sulfamethazine, which are commonly used as antibiotic drugs. Our aim was to understand the impact of the –CH3 substituent group on the pyrimidine ring and its potential as herbicide candidates. We examined the geometric and electronic structures using density functional theory with the M06-2X hybrid exchange–correlation functional, coupled with the 6-311++G(d, p) basis set, in the gas phase. These geometric parameters were then compared to crystallographic data for validation. The frontier molecular orbital energies were employed to predict chemical reactivity descriptors, while molecular electrostatic potentials and Fukui functions aided in identifying the reactive sites within the sulfonamides. To gain insights into the supramolecular arrangement, we conducted molecular topology analyses, including the Hirshfeld surface and quantum theory of atoms in molecules. These analyses revealed that the intermolecular interactions in the respective crystals are primarily closed-shell, characterized as van der Waals forces and hydrogen bonds. Additionally, the stability of these interactions was confirmed through natural bond orbital calculations. Furthermore, we carried out toxicophoric modeling against the acetolactate synthase enzyme to identify potential interacting groups. Molecular docking studies were carried out to examine the interactions of sulfonamides with the enzyme's binding site. The quantum theory of atoms in molecules was employed to gain insights into the nature of interactions between the toxicophoric groups and the lateral chains of amino acids present at the enzyme's binding site. Tests of Human Ether-a-go-go-Related Gene Inhibition, AMES Toxicity, Fish Toxicity, Tetrahymena Pyriformis toxicity, and honey bee toxicity showed that the sulfonamide derivatives do not cause toxicity in these species and may present good environmental tolerance. The results obtained in this study suggest the need for biological tests to validate the herbicidal potential of sulfonamides. [ABSTRACT FROM AUTHOR]