Sulfonamide Derivatives Research Articles

99mTc-labeled benzenesulfonamide derivative-entrapped gold citrate nanoparticles as an auspicious tumour targeting

Sulfonamide derivatives are a significant class of medicinal compounds. Gold nanoparticles (AuNPs) offer precise cancer treatment through targeted delivery, boasting high drug-loading capacity and low toxicity. This study aimed to develop and evaluate 99mTc-labeled benzenesulfonamide derivative-entrapped gold citrate nanoparticles as a tumor-targeting agent. A novel benzenesulfonamide derivative bearing a pyridine moiety was synthesized. Compound 3 (4-((3-cyano-4-(2,4-dichlorophenyl)-6-phenylpyridin-2-yl)amino)-N-(diaminomethylene)benzenesulfonamide) exhibited remarkable anti-cancer activity against MCF-7 cells. The chemical reduction method was employed to create compound 3-citrate-AuNPs. A comprehensive examination of the synthesized nano-platform was conducted, including zeta potential, size analysis, radiochemical yield, and in-vivo biodistribution in tumor-bearing mice. The nano-platform was successfully produced with good stability, optimal particle size (9 nm diameter for AuNPs), and high radiochemical purity for [99mTc]Tc-compound 3 (88.31 ± 2.14%). In-vivo investigations revealed that intravenously administered [99mTc]Tc-compound 3-citrate-AuNPs accumulated in tumors with a high target-to-non-target ratio. The findings validate the efficacy of the novel [99mTc]Tc-compound 3-citrate-AuNPs platform as a tumor-targeting agent.

Design, Synthesis, and Biological Evaluation of Novel Aryl Sulfonamide Derivatives as Potential Succinate Dehydrogenase Inhibitors Targeting Phytopathogenic Fungi.

In our pursuit of novel succinate dehydrogenase inhibitor (SDHI) fungicides for agriculture, we replaced the traditional amide structure with a sulfonamide framework and introduced various heterocyclic and aromatic rings at the sulfonamide's termini. This strategy yielded 30 synthesized compounds, which were screened for antifungal activity against eight phytopathogenic fungi. The biological assay results demonstrated that several target compounds exhibited significant in vitro antifungal activity. Notably, compound 2f showed remarkable antifungal activity against Valsa mali with an EC50 value of 0.56 mg/L, outperforming Boscalid (EC50 = 1.79 mg/L). In vivo experiments revealed that compound 2f provided significant protection to apple fruits, comparable to Boscalid. SEM analysis of compounds 2f and 3e showed that compound 2f disrupted the structure and morphology of fungal hypha analysis, which suggested that the terminal polyhalogen-substituted pyridine moieties might be pivotal regions influencing their antifungal efficacy. Molecular docking analysis revealed that compound 2f and Boscalid exhibited a comparable binding mode to SDH. Furthermore, detailed SDH inhibition assays confirmed the potential of 2f (IC50 = 2.51 μM) as prospective SDH inhibitors. RNA transcriptomic analysis indicated that the application of compound 2f could influence gene expression in fungi, thereby exerting a defensive effect against plant pathogenic fungi. Consequently, compound 2f shows promise for developing a novel and efficient agrochemical fungicide.

Crystallographic and computational characterization and in silico target fishing of six aromatic and aliphatic sulfonamide derivatives.

The molecular and crystal structures of six compounds containing sulfonamide moieties are described. It has been shown that the geometric parameters of the sulfonamide group depend little on the nature of the substituents. Their bond lengths and bond angles remain almost the same and are in good accordance with those known from the literature. In crystals, depending on the type of substituents the molecules exist in the form of either monomers or dimers joined by intermolecular hydrogen bonds involving sulfonamide fragments. Introduction of large substituents into the molecules changes the way of packing of the studied sulfonamides and decreases the number of intermolecular hydrogen bonds in the crystals. The value of this dihedral angle may affect the nature and strength of the intermolecular bonding of the species in crystals. In silico analyses predicted low toxicity and potential enzyme inhibition, along with antiprotozoal properties, suggesting these compounds as candidates against protozoan pathogens. Molecular docking confirmed inhibitory potential against trypanothione reductase, supporting antiprotozoal activity. Consequently, these compounds may serve as promising lead-like molecules for drug development targeting protozoan infections.

Synthesis and antitumor activity of new series of isopimaric heterocyclic sulfonamides derivatives

Synthesis and antitumor activity of new series of isopimaric heterocyclic sulfonamides derivatives

1,3,4-Oxadiazole Sulfonamide Derivatives Containing Pyrazole Structures: Design, Synthesis, Biological Activity Studies, and Mechanism Study.

Sulfonamide derivatives have been widely used for pesticide research in recent years. Herein, 1,3,4-oxadiazole sulfonamide derivatives containing a pyrazole structure were synthesized, and their structure-activity relationship was studied. Bioactivity tests showed the remarkable efficacy of most synthesized compounds. Especially for Xanthomonas oryzae pv oryzae, A23 exhibited 100% inhibition at 100 mg/L, surpassing bismerthiazol (99.3%), and 90% inhibition at 50 mg/L, outperforming thiodiazole copper (84.5%), with an EC50 of 5.0 mg/L, markedly more active than bismerthiazol (23.9 mg/L) and thiodiazole copper (63.5 mg/L). Initial investigations into antimicrobial mechanisms involved a series of biochemical analyses, including bacterial growth rate analysis, scanning electron microscopy, bacterial biofilm formation experiments, and molecular docking analyses. Notably, A23 considerably inhibited the formation of Xoo biofilms, disrupting the integrity of bacterial cell membranes. Co-analysis of transcriptomics and proteomics revealed the capability of A23 to regulate pathways such as tryptophan metabolism and phenylpropanoid biosynthesis, enhancing the innate immunity of rice and activating its disease resistance. Thus, A23 emerges as a potential immunoinducible pesticide lead compound for the discovery of highly active immune-inducing agents.

Novel Pyrimidinyl Sulfonamide Derivatives as GPR17 Modulators

Novel Pyrimidinyl Sulfonamide Derivatives as GPR17 Modulators

Tamarind seed gum-based hydrogel for the targeted delivery of imidazobenzothiazole sulfonamide derivative as an anticancer agent.

The current investigation intended to assess the controlled delivery of 7-sulfonamide-2-(4-methylphenyl) imidazo[2,1-b] [1, 3] benzothiazole an anticancer agent (ACA) by tamarind seed gum-based hydrogel; for its potential activity against hepatocellular carcinoma. The FTIR spectra, SEM, 13C NMR, PXRD, and TGA analyses evidenced the successful loading of ACA into the hydrogel system. The rheological testing conveyed the increase in the elastic nature of ACA-loaded hydrogel helping in an effective release. In-vitro delivery of ACA from the hydrogel matrix was maximum at pH 5.5 with controlled and prolonged release of 98.93 ± 1 % over 1680 min. The ACA-release kinetics was well-fitted to the Hill equation model (R2 = 0.9925), leading to a non-Fickian diffusion process (n = 0.5217). The tamarind seed gum-based hydrogel as a potential matrix for the oral administration of the ACA at hepatocellular carcinoma was envisaged and acute oral toxicity assessment on the Drosophila Melanogaster model indicated a high safety profile in-vivo. The ACA-loaded TG-g-poly (AMPS) system showed an enhanced anticancer activity with an IC50 value of 37.27 μg/mL than the ACA (IC50 = 44.75 μg/mL). Studies on the ACA-loaded hydrogel's ability to induce apoptosis in hepatocellular carcinoma cells further supported its anticancer effectiveness in-vitro.

Antiproliferative Activity and Molecular Docking of Some Pyrazole-Based Quinazolinone, Benzimidazole, and Tetrazinethione Derivatives.

Researchers are actively looking for novel anticancer medications because cancer is one of the leading causes of mortality worldwide. A fascinating area of study in medicinal chemistry is the screening of antioxidants for novel anticancer medicines, as antioxidants have lately been used as therapeutic candidates to combat a variety of ailments in aerobic species. Additionally, pyrazole-based heterocycle synthesis is a productive approach to the drug development process. To ascertain the molecular geometry and frontier orbital analysis, a DFT simulation of the produced compounds was conducted. Compound 7 showed the lowest energy gap and hardness, while compound 7 had the maximum softness. Therefore, a few quinazoline, benzimidazole, and tetrazinethione derivatives based on pyrazoles that were synthesized in our earlier work and exhibited antioxidant qualities were tested for their in vitro antiproliferative activity against the MCF7 and HCT116 cancer cell lines. The two cancer cell lines were most effectively inhibited by derivatives of sulfonamide and tetrazinethione. The molecular docking simulation toward CDK2 protein specified the best docking score of tetrazinethione 7 followed by sulfonamide derivative 4, compared to doxorubicin and roscovitine (kinase inhibitor). Most of the amino acids interacting with these compounds were involved in that interaction with the co-crystallized ligand. Their favorable oral bioavailability and drug-likeness characteristics were demonstrated by a modeling pharmacokinetics investigation. This research could help create novel antiproliferative drugs that are both efficient and selective.

A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents.

Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of Trypanosoma cruzi (α-TcCA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes. The aim of this study was to identify potential α-TcCA inhibitors with trypanocide activity. A maximum common substructure (MCS) and molecular docking were used to carry out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an in vitro model against the NINOA strain of Trypanosoma cruzi, and cytotoxicity was determined in a murine model of macrophage cells J774.2. Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-TcCA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC50) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of Trypanosoma cruzi. Compounds C7, C9, and C21 showed trypanocide activity; therefore, these results encourage the development of new trypanocidal agents based on their scaffold.

Design, Synthesis, and In Vitro Evaluation of Aromatic Sulfonamides as Human Carbonic Anhydrase I, II, IX, and XII Inhibitors and Their Antioxidant Activity.

This study is focused on the design, synthesis, and evaluation of some sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) enzymes I, II, IX, and XII as well as for their antioxidant activity. The purity of the synthesized molecules was confirmed by the HPLC purity analysis and was found in the range of 93%-100%. The inhibition constant (Ki) against hCA I ranged from 0.75 nM to 1972 nM. The sulfonamides inhibited isoform hCA II significantly, with a Ki ranging from 0.09 to 56 nM. Similarly, the inhibitory effects on hCA IX and XII were found with Ki spanning from 27.8 to 2099 nM and 9.43 to 509 nM, respectively. Most of the synthesized compounds showed significant inhibition in comparison to standard drugs such as acetazolamide, ethoxzolamide, zonisamide, methazolamide, dorzolamide, and SLC-0111. Antioxidant activity was assessed using the DPPH assay, with compound 13 showing better antioxidant activity with an IC50 of 54.8 µg/mL, as compared to the standard ascorbic acid (IC50 64.7 µg/mL). The molecular docking studies provided insights into the binding modes of these compounds. The in silico physicochemical properties, pharmacokinetic/ADME, and toxicity properties evaluations confirmed favorable drug-likeness properties, complying with Lipinski's rule. These findings underscore the therapeutic potential of these compounds for the treatment of retinal/cerebral edema, glaucoma, edema, epilepsy management, high-altitude sickness, and cancer.

Structural and Computational Insights into a Benzene Sulfonamide Derivative: Hirshfeld Surface, Energy Framework, Optical, NBO, Electronic and Biological properties

Structural and Computational Insights into a Benzene Sulfonamide Derivative: Hirshfeld Surface, Energy Framework, Optical, NBO, Electronic and Biological properties

Synthesis of 2-(4-Methyl-Phenoxymethyl) Benzoic Acid; Cresol and its Metal Coordinate Complexes

A series of phenoxymethylbenzoic acid derivatives were synthesized by reacting p-cresol with phthalide. The resulting phenoxymethyl benzoic acid was converted into corresponding acid chloride by reacting with cyanuric chloride. These phenoxymethyl benzoyl chlorides were then reacted with various aminobenzenesulfonamides and synthesize d new sulfonamide derivatives. The targeted sulfonamides were subjected to structural characterization by contemporary spectroscopic techniques like UV-visible and FT-IR. The presence of a peak at 3400/cm confirmed the existence of amide functionality, and furthermore , the broad peak at1250/cm showed that the sulfone group is present in the molecule.

Current development in sulfonamide derivatives to enable CNS-drug discovery.

The encouraging therapeutic potential of sulfonamide-based derivatives has been unraveled by breakthrough discovery of Paul Ehrlich, who pointed out the possibility of fighting microbes with chemicals. Over the decades, the utility of sulfonamides has expanded beyond antimicrobial agents, revealing their usefulness in many areas of pharmacotherapy, including the treatment of central nervous system (CNS) diseases. Through a detailed analysis of preclinical and clinical data, we identify key sulfonamide-based compounds that have demonstrated significant CNS activity. We also discuss the challenges in the development of sulfonamide derivatives as enzyme/ion channel inhibitors or receptor ligands for CNS applications, describing their mode of action and therapeutic significance. This is followed by the characteristics of pharmacological targets, structure-activity relationships, ADMET properties, efficacy in experimental animal models, and outcomes from clinical trials. Overall, the versatile nature of arylsulfonamides makes them a valuable motif in drug discovery, offering diverse opportunities for the development of novel agents for treating CNS disorders.

Exploring aliphatic sulfonamides as multiclass inhibitors of the carbonic anhydrases from the pathogen bacterium Vibrio cholerae.

This study investigates aliphatic sulfonamide derivatives as inhibitors of the α-, β-, and γ-class carbonic anhydrase (CA) isoforms from Vibrio cholerae (VchCAs). A series of 26 compounds bearing a triazole linker and urea- or ether-based tails were described and evaluated for their inhibitory action using a stopped-flow CO2 hydrase technique. These inhibitors demonstrated a preferential efficacy against VchCAβ. Specifically, the ureido derivatives showed the highest inhibitory potency with inhibition constants (KIs) in the submicromolar range (0.67-0.93 µM). Selectivity indices were calculated to assess the selective inhibition of VchCAβ over human CA I and II, as well as other VchCA isozymes. Urea-linked compounds demonstrated a significant 25- to 125-fold selectivity for VchCAβ over hCAs and 14- to 26-fold over other VchCAs. Molecular modeling elucidated the interactions contributing to the efficacy and selectivity of aliphatic sulfonamides as VchCA inhibitors, aligning with and reinforcing the experimental results. The latter suggests that aliphatic sulfonamides could serve as valid targeted therapeutics to treat V. cholerae infections.

Discovery of Novel Inhibitors Against Resistant Streptococcus pneumoniae MurF Enzyme using Phamracophore Modeling and QSAR Analysis

Main aim of the current study was to discover novel inhibitors against Streptococcus pneumoniae MurF enzyme using analogue based drug design. Pharmacophore mapping and 3D-QSAR analysis was performed on some previously synthesized and evaluated sulfonamide derivatives which are known to be potent inhibitors of penicillin resistant Streptococcus pneumoniae MurF receptor. 3D-QSAR study based on the principle of alignment of pharmacophoric features was performed on the same set of inhibitors using the PHASE module of Schrodinger suite. A five point pharmacophore, ADHRR, with one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic group and two aromatic rings yielded a statistically significant 3D-QSAR model with 0.96 as R2 value for three PLS components and good predictive correlation coefficients of Q2 = 0.8084, F = 140.6 and Pearson-R = 0.9157 for the test set with nine compounds. Thus, indicating good predictive power of the pharmacophore based 3D-QSAR model.

Synthesis and in vitro antimicrobial screening of some 5-methyl-2-substituted phenyl-3- (phenylsulfonyl)thiazolidin-4-ones

The synthesis of some new thiazolidine-sulfonamide derivatives was achieved in two steps. In the first step, appropriate aryl aldehyde reacted with benzene sulfonamide to yield N-arylidene benzene sulfonamide derivatives (1a-h). In the second step, compounds (1a-h) reacted with thiolactic acid to give the 5-methyl-2-substituted phenyl-3-(phenylsulfonyl) thiazolidin-4-one derivatives (2a-h). The compounds 2a-h were screened for their in vitro antimicrobial activity by agar disc diffusion method. The results showed that compounds 2b, 2c, and 2d exhibited anti-microbial activity against the tested both Gram-positive and Gram-negative bacterial strains and compounds 2c, 2d, and 2g exhibited significant antifungal activity against fungal strains. The antimicrobial activity of tested compounds was compared with the standard antimicrobial drug ampicillin and antifungal drug clotrimazole.. KEYWORDS :Thiazolidines, Sulphonamides, Antimicrobial, N-Arylidene benzene sulfonamide.

Integrating morphology, physiology, and computer simulation to reveal the toxicity mechanism of eco-friendly rosin-based pesticides

To mitigate the impact of traditional chemical pesticides on environment, and achieve sustainable crop protection, 24 eco-friendly rosin-based sulfonamide derivatives were synthesized and developed. The in vitro activity assessment showed that compound 4X (Co. 4X) exhibited excellent fungicidal activity against V. mali (EC50 = 1.106 μg/mL), marginally surpassing the positive control carbendazim (EC50 = 1.353 μg/mL). In vivo investigations suggested that Co. 4X exhibited moderate efficacy in mitigating V. mali infection in both apple trees and apples. Physiological assessments revealed that Co. 4X induced severe ultrastructural damage to the mycelium, heightened cell membrane permeability, and inhibited SDH protein activity. Subsequent biosafety evaluations affirmed the environment-friendly of Co. 4X on Zebrafish (LC50(96h) = 25.176 μg/mL). Toxicological research revealed that Co. 4X caused damage to the cells of Zebrafish gills, liver, and intestines, resulting in impaired respiratory, detoxification, digestion, and absorption functions of Zebrafish. In summary, the findings of this study contribute to a deeper understanding of the toxicity mechanisms of novel pesticides, decreasing environmental risks caused by traditional chemical pesticides, and improving the effective management of novel pesticide applications.

Novel hole transport materials of pyrogallol-sulfonamide hybrid: synthesis, optical, electrochemical properties and molecular modelling for perovskite solar cells

Sulfonamide derivatives as semiconductor materials for organic optoelectronic devices, including photovoltaic (PV), have received considerable interest. In the present work, the synthesis of novel pyrogallol-sulfonamide derivatives based on a molecular hybridization approach yielded N-((4-((2,3,4-trihydroxyphenyl)diazenyl)phenyl)sulfonyl)acetamide (N-DPSA). The techniques of spectroscopy, Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), and mass spectrum were utilized to identify the structural composition of the synthesized N-DPSA. The new N-DPSA was investigated by Hall-effect measurement to prove the positive charge carrier (hole mobility) with mobility and conductivity of 2.39 × 103 cm2/Vs and 1.76 × 10–1 1/Ω cm, respectively. Consequently, N-DPSA could be proposed as a strong candidate as a p-type semiconductor (hole transport layer (HTL)). The optical energy gap was computed at 2.03 eV, indicating the direct optical transition nature of N-DPSA. The elaborated molecular semiconductor's thermal features, molecular modelling, and electronic energy levels were also investigated. The new N-DPSA at various concentrations provided easy synthesis, cheap cost, high performance, and a straightforward design approach for a possible HTL in effective perovskite solar cells (PSCs). A PCE of 7.3% is shown for the N-DPSA-based PSC at its optimal concentration.

Overview on Design and Synthesis of Sulfonamide Derivative through Condensation of Amino Group Containing Drug

In medicinal and non-pharmacological chemistry, sulfonamides (SN) are an advisory functional group that forms the basis of many drugs. As such, they are very important. Recently, very significant techniques for the synthesis of sulfonamides have been developed. Numerous pharmacologic activities, including anti-dydropteroate synthetase and anti-carbonic anhydrase, are displayed by sulfonamides. Derivatives of sulfonamides can be used to treat a range of medical conditions, including glaucoma, hypoglycemia, stasis, diarrhea, and inflammation. Our current work has concentrated on creating and synthesizing sulfonamide derivatives via condensation reaction between amino group-containingdrugs.The functionality of sulfonamideinthe clinical trial for the treatment of various medical conditions. For these reasons, development of an efficient process for the synthesis of sulfonamides has always been in the focus for research in organic field synthesis. The most typical method for the synthesis involves reaction between primary or secondary amines and sulfonyl chloride in presence of organic or inorganic bases. Although this method is effective, but the nucleophilicity of amines may vary depending on the groups attached to it. In general, primary amines are highly reactive, whereas secondary amines show very low to almost nil reactivity. In this study, we have reviewed past and recent biological effects of some sulfonamide derivatives and some advances efficient synthetic procedures for some types of sulfonamides. A sulfonamide is a functional group that is the basis of several sulfa drugs and thereby are very much important scaffolds in medicinal as well as in synthetic organic chemistry. Recently very important methodologies have been developed for the synthesis of sulfonamide. This complex review article covers the recent developments (mainly in period 2013- 2019) of powerful methodologies for the synthesis of sulfonamide compounds, particularly where SO2N(R) moiety is not present in a cyclic structure and their applications in various fields during this period. A critical view of the mechanisms of the developed methodologies together with the scope and limitation of these methods adds an extra dimension to the text

Molecular docking, ADME properties and synthesis of thiophene sulfonamide derivatives

This study investigates the drug-like properties of target molecules containing thiophene sulfonamide groups (7a–7s) using computational molecular docking techniques. The binding interactions of these derivatives were assessed using protein 2NSD (Enoyl acyl carrier protein reductase InhA, complexed with N-(4-methylbenzoyl)-4-benzylpiperidine, PDB DOI: 10.2210/pdb2NSD/pdb) as the receptor. Molecular docking results revealed notable docking scores for all compounds, ranging from −6 to −12 kcal/mol. Compounds 7e, 7i, and 7f, in particular, demonstrated impressive glide scores (>11 kcal/mol) and were selected for further analysis through molecular dynamics simulations, which provided deeper insights into their dynamic behavior and stability. The drug-like properties of these molecules were evaluated based on Lipinski’s Rule of Five and ADME (Absorption, Distribution, Metabolism, and Excretion) criteria and compared with known drugs. Additionally, we synthesized these target molecules (7a–7s) using Suzuki-Miyaura coupling with a nickel catalyst replacing palladium. The chemical structures of the synthesized compounds were confirmed through elemental analysis, LC-MS,1H-NMR, and 13C-NMR spectroscopy.