Sulfonamide Functional Group Research Articles

Novel inhibitor N-cyclopropyl-4-((4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)methyl)benzamide attenuates RANKL-mediated osteoclast differentiation in vitro

Both cyclopropyl amide and piperazine sulfonamide functional groups are known for their various biological properties used for drug development. Herein, we synthesized nine new derivatives with different substituent groups incorporating these moieties and screened them for their anti-osteoclast differentiation activity. After analyzing the structure–activity relationship (SAR), the inhibitory effect against osteoclastogenesis was determined to be dependent on the lipophilicity of the compound. Derivative 5b emerged as the most effective dose-dependent inhibitor after TRAP staining with an IC50 of 0.64 µM against RANKL-induced osteoclast cells. 5b was also able to suppress F-acting ring formation and bone resorption activity of osteoclasts in vitro. Finally, well-acknowledged gene and protein osteoclast-specific marker expression levels were decreased after 5b administration on primary murine osteoclast cells.

π-Clamp-Mediated Homo- and Heterodimerization of Single-Domain Antibodies via Site-Specific Homobifunctional Conjugation.

Post-translational protein–protein conjugation produces bioconjugates that are unavailable via genetic fusion approaches. A method for preparing protein–protein conjugates using π-clamp-mediated cysteine arylation with pentafluorophenyl sulfonamide functional groups is described. Two computationally designed antibodies targeting the SARS-CoV-2 receptor binding domain were produced (KD = 146, 581 nM) with a π-clamp sequence near the C-terminus and dimerized using this method to provide a 10–60-fold increase in binding (KD = 8–15 nM). When two solvent-exposed cysteine residues were present on the second protein domain, the π-clamp cysteine residue was selectively modified over an Asp-Cys-Glu cysteine residue, allowing for subsequent small-molecule conjugation. With this strategy, we build molecule–protein–protein conjugates with complete chemical control over the sites of modification.

Photocatalytic Late-Stage Functionalization of Sulfonamides via Sulfonyl Radical Intermediates.

A plethora of drug molecules and agrochemicals contain the sulfonamide functional group. However, sulfonamides are seldom viewed as synthetically useful functional groups. To confront this limitation, a late-stage functionalization strategy is described, which allows sulfonamides to be converted to pivotal sulfonyl radical intermediates. This methodology exploits a metal-free photocatalytic approach to access radical chemistry, which is harnessed by combining pharmaceutically relevant sulfonamides with an assortment of alkene fragments. Additionally, the sulfinate anion can be readily obtained, further broadening the options for sulfonamide functionalization. Mechanistic studies suggest that energy-transfer catalysis (EnT) is in operation.

N,N-Dimethylethanesulfonamide as an Electrolyte Solvent Stable for the Positive Electrode Reaction of Aprotic Li–O2 Batteries

The realization of secondary lithium–oxygen batteries (Li–O2 batteries, LOBs) with large gravimetric energy density requires the development of an innovative electrolyte with high chemical stability that allows the charge–discharge reaction to proceed with low overvoltage. In this study, we evaluated the potential of an electrolyte solvent, N,N-dimethylethanesulfonamide (DMESA) with a sulfonamide functional group, at a current density of 0.4 mA cm–2 and a capacity of 4 mA h cm–2. The voltage at which CO2 was generated during charging was substantially higher than that of a tetraglyme (G4)-based electrolyte with redox mediators, which is one of the standard electrolytes used for LOBs. Experiments using a 13C-containing positive electrode revealed that CO2 generated during charging mainly originated from the decomposition of the positive electrode. The analyses of the charging profile in conjunction with differential electrochemical mass spectrometry suggested the formation of highly degradable lithium peroxide (Li2O2) in the DMESA-based electrolyte. The formation of highly degradable Li2O2 enables a reduction of the charging voltage, leading to further suppression of the electrolyte decomposition.

Comparative study on qualitative and quantitative analysis of Inji Charu (Ginger Juice) and Inji Surasam (Ginger Decantent) prepared as per The Siddha literature

Therapeutic aspects of Siddha consist of herbal or poly herbal, mineral, metal and animal products which given specific vehicle. Some of the herbal drugs which are used as vehicle may be processed before administration. Among these the Inji Charu (Ginger Juice) (Zinger officinale Roscoe) is commonly used as Anupanam (vehicle). Inji Charu has more volatile oils which produce pungent effect, so the process of Inji surasam (Ginger Decantent) will reduce the concentration of volatile oils and mitigate the pungent effect. Objective of the study is comparing the chemical constitution of Inji surasam and Inji Charu was analyzed by HPTLC and FTIR. The study result, Concentration of the major chemical compounds was quality wise same and quantity wise differ in both sample found. Alkyl aryl ether, Anhydride functional group were only present in Inji charu and Alkyne Nitro, Sulfonate, Sulfonic Acid, Sulfoxide, Sulfonamide functional group were only present in Inji Surasam.

Quinolinyl sulfonamides and sulphonyl esters exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)

The “superbug” infection caused by metallo-β-lactamases (MβLs) has grown into anemergent health threat, and development of effective MβL inhibitors to restore existing antibiotic efficacy is an ideal alternative. Although the serine-β-lactamase inhibitors have been used in clinical settings, MβL inhibitors are not available to date. In this work, thirty-one quinolinyl sulfonamides 1a-p and sulphonyl esters 2a-o were synthesized and assayed against MβL NDM-1. The obtained molecules specifically inhibited NDM-1, 1a-p and 2a-o exhibited an IC50 value in the range of 0.02–1.4 and 8.3–24.8 μM, respectively, and 1e and 1f were found to be the most potent inhibitors, with an IC50 of 0.02 μM using meropenem (MER) as substrate. Structure-activity relationship reveals that the substitute phenyl and the phenyl with a halogen atom more significantly improve inhibitory effect of quinolinederivatives on NDM-1. 1a-p restored antimicrobial effect of MER on E. coli with NDM-1, EC01 and EC08, resulting in a 2–64-fold reduction in MIC values. Most importantly, 1e synergized MER and significantly reduced the load of EC08 in the spleen and liver of mice after a single intraperitoneal dose. Docking studies suggested that the endocyclic nitrogen of the quinoline ring, and exocyclic nitrogen of the sulfonamide functional group are coordinate with Zn(II) ion at active sites of NDM-1. Cytotoxicity assays indicated that 1e had low cytotoxicity. This work offers potential lead compounds for further development of the clinically useful inhibitor targeting NDM-1.

Acetylenic Sulfones and Acetylenic Sulfonamide Analogs: A Novel and Preferable Antimicrobial Drugs Based on Computational Strategies

This study was done to report virtual screening and molecular docking studies of sulfacetamide derivatives as new antimicrobial drugs, belonging to the pharmacological class of sulfonamides. For this purpose, sulfonamide functional groups from a library of chemical structures were converted into acetylenic sulfone and acetylenic sulfonamide functional groups to introduce a new class of antimicrobial drugs with mechanisms of action of dihydropteroate synthase inhibitors (DHPS). Initially, a library of compounds containing approximately 170 acetylenic sulfone ligands was created by similarity search method, and a library containing 170 acetylenic sulfonamide ligands was designed to be administered as new inhibitors. After designing, their molecular docking energies were calculated by three software programs including Arguslab4.0.1, AutoDock Vina and Molegro Virtual Docker and the results were compared in terms of binding energy. Although acetylenic sulfonamide compounds showed better results, acceptable results were observed in both groups of compounds. Adsorption, distribution, metabolism and excretion (ADME) properties of acetylenic sulfones/acetylenic sulfonamide analogs were also analyzed using the admetSAR program. These new derivatives can be used in drug improvement processes for the treatment of antibacterial infections after performing further studies.

Determination of Antibacterial Properties of Some Sulfonamide Compounds by Molecular Docking

Prontosil, the sulfonamide compound that started the antibacterial era, was the first commercially available antibacterial agent. Sulfonamide functional groups have gained importance in medicinal chemistry since the first announcement of antibacterial drugs. Synthetic sulfonamides are generally used for the treatment of bacterial infections in biological systems, as well as antifungal, anti-inflammatory antioxidant, diuretics, carbonic anhydrases, antitumor and so on. It has aroused high curiosity in biology and medicine due to its wide range of biological applications. In this study, molecular docking studies were applied to investigate the potential antibacterial properties of sulfonamide derivative compounds synthesized in previous study. The binding energies was anaylzed by Autodock 4.2 code which also performed molecular docking. Docking simulations of sulfonamide compounds at the active site of E. coli β-ketoacyl-acyl carrier protein synthase III (KAS III, PDB ID: 1HNJ) were performed to determine possible binding patterns and inhibitory effects. Docking results were also compared with triclosan used as a commercial antibacterial agent. Biovia Discovery Studio Visualizer 2020 and Autodock 4.2 software were used to analyze results of molecular docking.The binding energies of 3, 4, 5 and 6 sulfonamides used in the study to KAS III enzyme were found to be -6.94, -7.22, -7.76, -8.13, respectively. As a result of molecular docking study, these sulfonamide derivatives may have potential antibacterial properties.

Accurate acid dissociation constant (pKa) calculation for the sulfachloropyridazine and similar molecules.

Accurate calculation of the acid dissociation constant (pKa) has fundamental importance for the description of molecular systems with pharmacological activities. The search for a more appropriate procedure for its determination is always welcome and has aroused increasing interest from the scientific community. In this sense, this work presents a computational study involving the combination of ten DFT functionals (M062X, M06L, B3LYP, BLYP, PBEPBE, BP86, LC-BLYP, SPBE, CAM-B3LYP, LC-PBEPBE) and HF method, eight basis set functions (6-311G, 6-311 + G, 6-311G(d,p), 6-311 + G(d,p), 6-311+ +G(d,p), 6-311(2d,2p), 6-311+ +G(2d,2p), and aug-cc-pVDZ), and three solvation models (SMD, PCM, and CPCM) for an accurate sulfachloropyridazine (SCR) pKa determination. It was found that the smallest deviation (0.02 unit of pKa) between the current study and experimental result was achieved with the BLYP/6-311 + G(d,p)/PCM combination. Therefore, this combination was extended to calculate the pKa of six SCR similar molecules selected through the eletroshape similarity method. For all these molecules, the difference between the obtained results and experimental data ranged between 0.14 and 0.69 units of pKa. This feature suggests that the obtained combination can determine pKa with experimental precision for complexes that are formed by sulfonamide functional group (SO2NHR). Graphical Abstract A computational study involving the combination of different levels of theory, basis sets and solvation models for an accurate sulfanamide pKa determination.

Organocatalytic Stereoselective [8+2] Cycloaddition of Tropones with Azlactones

Organocatalytic Stereoselective [8+2] Cycloaddition of Tropones with Azlactones

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.

Acid‐Promoted Expeditious Syntheses of Aminated Dibenzosultams via Palladium/Norbornene Cooperatively Catalysed C−H Amination/Arylation

AbstractHerein we reported a protocol to access aminated benzofused sultams through sequential ortho‐amination, followed by ipso‐arylation of aryl iodide bearing sulfonamide functional group via palladium/norbornene coorperative catalysis. This reaction has showcased a broad spectrum of substrate scope under mild conditions with moderate to good efficiency.magnified image

Microbial Interactions Drive the Complete Catabolism of the Antibiotic Sulfamethoxazole in Activated Sludge Microbiomes.

Microbial communities are believed to outperform monocultures in the complete catabolism of organic pollutants via reduced metabolic burden and increased robustness to environmental challenges; however, the interaction mechanism in functional microbiomes remains poorly understood. Here, three functionally differentiated activated sludge microbiomes (S1: complete catabolism of sulfamethoxazole (SMX); S2: complete catabolism of the phenyl part of SMX ([phenyl]-SMX) with stable accumulation of its heterocyclic product 3-amino-5-methylisoxazole (3A5MI); A: complete catabolism of 3A5MI rather than [phenyl]-SMX) were enriched. Combining time-series cultivation-independent microbial community analysis, DNA-stable isotope probing, molecular ecological network analysis, and cultivation-dependent function verification, we identified key players involved in the SMX degradation process. Paenarthrobacter and Nocardioides were primary degraders for the initial cleavage of the sulfonamide functional group (-C-S-N- bond) and 3A5MI degradation, respectively. Complete catabolism of SMX was achieved by their cross-feeding. The co-culture of Nocardioides, Acidovorax, and Sphingobium demonstrated that the nondegraders Acidovorax and Sphingobium were involved in the enhancement of 3A5MI degradation. Moreover, we unraveled the internal labor division patterns and connections among the active members centered on the two primary degraders. Overall, the proposed methodology is promisingly applicable and would help generate mechanistic, predictive, and operational understanding of the collaborative biodegradation of various contaminants. This study provides useful information for synthetic activated sludge microbiomes with optimized environmental functions.

Synthesis Crystal Structure and Spectral Properties of New Sulfonamides

In this paper, we report new sulfonamide derivatives, 4-((2,4-dichlorophenylsulfonamido)methyl)cyclohexanecarboxylic acid (1), ethyl 4-((naphthalene-2-sulfonamido)methyl)cyclohexanecarboxylate (2), and ethyl 4-((2,5-dichlorophenylsulfonamido)methyl)cyclohexanecarboxylate (3). The compounds were and characterized by FTIR, ESI-MS, and X-ray crystallography. Single crystal X-ray diffraction analysis shows that 1 crystallizes in the orthorhombic space group Pbcn, 2 in the monoclinic space group Cc and 3 in the monoclinic space group Cc. All three molecules feature hydrogen bonding. Three sulfonamide derivatives, 4-((2,4-dichlorophenylsulfonamido)methyl)cyclohexanecarboxylic acid (1), ethyl 4-((naphthalene-2-sulfonamido)methyl)cyclohexanecarboxylate (2) and ethyl 4-((2,5-dichlorophenylsulfonamido) methyl)cyclo-hexanecarboxylate (3) have been synthesized and their structures confirmed by single crystal X-ray diffraction. Hydrogen bonding in compound 1 involves carboxylic groups and N–H moieties as well as non-classical C–H···O interactions, while in 2 and 3, the N–H moiety and an oxygen atom of the sulfonamide functional group of neighboring molecules are involved.

Crystal structure of 4-methyl-N-propyl-benzene-sulfonamide.

The crystal structure of the title sulfonamide, C10H15NO2S, comprises two mol-ecules in the asymmetric unit. The S=O bond lengths of the sulfonamide functional group range from 1.428 (2) to 1.441 (2) Å, with S-C bond lengths of 1.766 (3) Å (for both mol-ecules in the asymmetric unit), and S-N bond lengths of 1.618 (2) and 1.622 (3) Å, respectively. When both mol-ecules are viewed down the N-S bond, the propyl group is gauche to the toluene moiety. In the crystal structure, mol-ecules of the title compound are arranged in an intricate three-dimensional network that is formed via inter-molecular C-H⋯O and N-H⋯O hydrogen bonds. The crystal structure was refined from a crystal twinned by inversion.

Crystal structure of N,N-diisopropyl-4-methyl-benzene-sulfonamide.

The synthesis of the title compound, C13H21NO2S, is reported here along with its crystal structure. This compound crystallizes with two mol-ecules in the asymmetric unit. The sulfonamide functional group of this structure features S=O bond lengths ranging from 1.433 (3) to 1.439 (3) Å, S-C bond lengths of 1.777 (3) and 1.773 (4) Å, and S-N bond lengths of 1.622 (3) and 1.624 (3) Å. When viewing the mol-ecules down the S-N bond, the isopropyl groups are gauche to the aromatic ring. On each mol-ecule, two methyl hydrogen atoms of one isopropyl group are engaged in intra-molecular C-H⋯O hydrogen bonds with a nearby sulfonamide oxygen atom. Inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions link mol-ecules of the title compound in the solid state.

A new chemotype with promise against Trypanosoma cruzi

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

Supramolecular synthon hierarchy in sulfonamide cocrystals with syn-amides and N-oxides.

Sulfonamide drugs are well known antibacterial and antimicrobial molecules for pharmaceutical development. Building a library of suitable supramolecular synthons for the sulfonamide functional group and understanding their crystal structures with partner coformer molecules continues to be a challenge in crystal engineering. Although a few sulfonamide cocrystals with amides and N-oxides have been reported, the body of work on sulfonamide synthons is limited compared with those that have carb-oxy-lic acids and carboxamides. To address this structural gap, the present work is primarily focused on sulfonamide-lactam and sulfonamide-syn-amide synthons with drugs such as celecoxib, hydro-chloro-thia-zide and furosemide. Furthermore, the electrostatic potential of previously reported cocrystals has been recalculated to show that the negative electrostatic potential on the lactam and syn-amide O atom is higher compared with the charge on carboxamide and pyridine N-oxide O atoms. The potential of sulfonamide molecules to form cocrystals with syn-amides and lactams are evaluated in terms of the electrostatic potential energy for the designed supramolecular synthons.

Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides

First introduced into medicines in the 1930s, the sulfonamide functional group continues to be present in a wide range of contemporary pharmaceuticals and agrochemicals. Despite their popularity in the design of modern bioactive molecules, the underpinning methods for sulfonamide synthesis are essentially unchanged since their introduction, and rely on the use of starting materials with preinstalled sulfur-functionality. Herein we report a direct single-step synthesis of sulfonamides that combines two of the largest monomer sets available in discovery chemistry, (hetero)aryl boronic acids and amines, along with sulfur dioxide, using a Cu(II) catalyst, to deliver a broad range of sulfonamides. Sulfur dioxide is provided by the surrogate reagent DABSO. The reaction tolerates broad variation in both coupling partners, including aryl, heteroaryl and alkenyl boronic acids, as well as cyclic and acyclic alkyl secondary amines, and primary anilines. We validate the method by showing that a variety of drugs, and drug-fragments, can be incorporated into the process.

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.