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Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7–9, 11–13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure–activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

Carbonic anhydrase (CA) isozymes participate in numerous pathological and physiological pathways. In this research, sulfonamide derivatives (QD and RD) of polyphenolic compounds quercetin (Q) and resveratrol (R) were chemically synthesized and their interaction with hCA II and CA IX isozymes was investigated. Data collection was performed experimentally using spectroscopic methods. As a result, all compounds were generally effective low micromolar CA competitive inhibitors. Among them, the sulfonamide derivative of quercetin (QD) had the lowest IC50 value (5.13 ± 0.24 µM) for the hCA II, which was lower than that of CA IX (28.52 ± 0.12 µM). Concerning the hCA II isozyme, the calculated Ki values for Q, QD, R, and RD compounds were 5.43 ± 0.65, 3.42 ± 0.26, 455.00 ± 12.02 and 242.50 ± 18.38 µM, respectively. Also, fluorescence measurements showed dynamic quenching of the hCA II intrinsic fluorescence. Moreover, evaluation of the thermodynamic parameters involved in binding revealed that both hydrogen bonds and van der Waals interactions are crucial in the interaction between these compounds and the hCA II isozyme. Fluorescence analysis of the CAII-DNSA fluorescent complex in different concentrations of Q, QD, R, and RD compounds showed the lowest dissociation constant (Kd) for the QD, indicating that this compound has a higher affinity for binding to the hCA II isozyme. Overall, the strengthening of the binding power and inhibitory activity of RD and QD for the hCA II and CA IX as compared to Q and R paves the way for the development of novel hCA inhibitors through the use of these derivatives. [ABSTRACT FROM AUTHOR]

A total of 66 sulfonamide derivatives bearing the 4-aminoquinazoline moiety were designed and synthesized, and their structures were fully characterized by 1H NMR, 13C NMR, and HRMS techniques. Among them, the structures of compounds 5A10 and 5B11 were further confirmed through X-ray single-crystal diffraction analyses. The bioassay results indicated that some of the target compounds displayed higher inhibition activities in vitro against the tested phytopathogenic bacteria. For example, compound 5A26 exhibited a strong anti-Xanthomonas oryzae pv. oryzicola (Xoc) efficacy with an EC50 (half-maximal effective concentration) value of 30.6 μg/mL, over twofold more active than control agent bismerthiazol (BMT). Additionally, compound 5B14 had a good antibacterial effect against the phytopathogen Xanthomonas axonopodis pv. citric (Xac) with EC50 = 34.5 μg/mL, significantly better than control agent BMT (71.5 μg/mL). The anti-Xoc mechanistic studies showed that compound 5A26 exerted its antibacterial efficacy by increasing the permeability of bacterial membrane, decreasing the content of extracellular polysaccharides, and triggering morphological changes of bacterial cells. [ABSTRACT FROM AUTHOR]

The electrochemical oxidation of clonazepam (CLNP) has been studied in presence of some aryl sulfinic acids as nucleophiles in aqueous buffered solution by means of cyclic voltammetry, and controlled- potential coulometry. Voltammetric studies of electrochemical behavior of clonazepam have also been investigated in different pH values (pH 1.0 to 10.0) in absence and presence of toluenesulfinic acid (1a) as well as benzenesulfinic acid (1b). The results indicated that peak current and peak potential depends on the level of pH. Finally, the synthetizing new sulfonamide derivatives was conducted through constant current electrolysis of clonazepam in presence of arylsulfinic acids at carbon rod electrodes, employing a green electrochemical protocol. CLNP which has cathodically produced hydroxylamine species is oxidized at the anode to generate nitroso species, participate in reaction with the arylsulfinic acids, converts it to the corresponding new sulfonamide derivatives. The new products have been characterized by IR, MS, 1H NMR and 13C NMR methods.

The two azo dye ligands named 4‐(2,4‐dihydroxy‐5‐formylphen‐1‐ylazo)‐N‐thiazol‐2‐yl‐benzenesulfon amide (H3TPBS) and 4‐(2,4‐dihydroxy‐phenylazo)‐N‐(3,4‐dimethyl‐1,2‐oxazol‐5 yl)benzenesulfonamide (H3IPBS) were employed for the synthesis of a series of Cu(II) chelates through the reaction of the ligands with Cu(II) salts of different anions. Full structure affirmation of all complexes has been done. Analytical results confirmed the formation of the metal chelates in the molar ratio 2:1 (M:L). Ultraviolet–visible spectra and magnetic moment proved the formation of complexes in square planar and square pyramidal geometries. Antimicrobic activity of the synthesized complexes has been assigned and compared with their parent ligands and also compared with standard antibiotic drugs showing enhanced activity over both the ligands and the standard drugs. The antitumor efficacy of the complexes has been also evaluated contra the two cell lines A‐549 cells (human Lung cancer cell line) and Panc‐1 (Pancreatic carcinoma) and compared with the standard drug Vinblastine. Additionally, The Cu(II) chelates were examined for their activity in oxidation coupling of o‐aminophenol (OAP) to 2‐aminophenoxazine‐3‐one (APX) in DMF solvent in open air atmosphere. The examined complexes afforded low to relatively high efficiency with TOF number from 0.27–78.12 h−1 with increased activity for complexes 1, 3, 5 and 7 incorporating Cl− or NO3− anions in their first coordination sphere. [ABSTRACT FROM AUTHOR]

Three novel copper(II)-based complexes Cu-1, Cu-2, and Cu-3 containing sulfamethoxazole or sulfamethazine ligand were obtained, and their single structures were characterized. Both Cu-1 and Cu-3 show a broad spectrum of cytotoxicity than Cu-2, and Cu-1 is more cytotoxic than Cu-3. What's interesting is that Cu-1 can exhibit obvious inhibitory effect on the growth of human triple-negative breast cancer in vivo and vitro through anti-proliferative, anti-angiogenic, anti-inflammatory, pro-apoptotic and cuproptotic synergistic effects. Though Cu-3 shows no significant cytotoxicity against MDA-MB-231 cells, it can significantly inhibit the growth of SKOV3 cells in vitro by down-regulating the expression of some key proteins in the VEGF/VEGFR2 signaling pathway and the expression of some pro-inflammatory cytokines, and by disrupting the balance of intracellular reactive oxygen species levels., Competing Interests: Declaration of competing interest Titled“Syntheses, crystal structures of copper (II)-based complexes of sulfonamide derivatives and their anticancer effects through the synergistic effect of anti-angiogenesis, anti-inflammation, pro-apoptosis and cuproptosis” This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All authors have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The retinoid-related orphan receptor gamma-t (RORγt), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor. As a pivotal modulator in the development and functionality of T-helper 17 (Th17) cells, RORγt plays a crucial role in immune response regulation. Inverse agonists targeting RORγt demonstrate significant potential in modulating Th17 cell activity, offering a promising avenue for the development of therapeutics aimed at treating autoimmune diseases associated with Th17 dysregulation. GSK2981278 is a potent RORγt inverse agonist, but a drawback of GSK2981278 is its low pharmacokinetic profile, leading to a clinical failure. We have explored detailed structure-activity relationship of GSK2981278 trying to improve metabolic stability while maintaining RORγt activity. As a result, a novel series of sulfonamide derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. b14 had greatly improved In Vitro metabolic stability (T 1/2  = 36.2 min) compared to GSK2981278 (T 1/2  = 0.8 min). Oral dosing of compound b14 resulted in a dose-dependent suppression of IL-17A cytokine levels within a murine model of imiquimod-induced skin inflammation, underscoring its potential as a therapeutic intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acute myeloid leukemia, a serious condition affecting stem cells, drives uncontrollable myeloblast proliferation, leading to accumulation. Extensive research seeks rapid, effective chemotherapeutics. A potential option is a BRD4 inhibitor, known for suppressing cell proliferation. Sulfonamide derivatives probed essential structural elements for potent BRD4 inhibitors. To achieve this goal, we employed 3D-QSAR molecular modeling techniques, including CoMFA, CoMSIA, and HQSAR models, along with molecular docking and molecular dynamics simulations. The validation of the 2D/3D QSAR models, both internally and externally, underscores their robustness and reliability. The contour plots derived from CoMFA, CoMSIA, and HQSAR analyses played a pivotal role in shaping the design of effective BRD4 inhibitors. Importantly, our findings highlight the advantageous impact of incorporating bulkier substituents on the pyridinone ring and hydrophobic/electrostatic substituents on the methoxy-substituted phenyl ring, enhancing interactions with the BRD4 target. The interaction mode of the new compounds with the BRD4 receptor (PDB ID: 4BJX) was investigated using molecular docking simulations, revealing favorable binding energies, supported by the formation of hydrogen and hydrophobic bonds with key protein residues. Moreover, these novel inhibitors exhibited good oral bioavailability and demonstrated non-toxic properties based on ADMET analysis. Furthermore, the newly designed compounds along with the most active one from series 58, underwent a molecular dynamics simulation to analyze their behavior. The simulation provided additional evidence to support the molecular docking results, confirming the sustained stability of the analyzed molecules over the trajectory. This outcome could serve as a valuable reference for designing and developing novel and effective BRD4 inhibitors.Communicated by Ramaswamy H. Sarma.

Sulfonamides are a classic group of chemotherapeutic drugs with a broad spectrum of pharmacological action, including anticancer activity. In this work, reversed-phase high-performance liquid chromatography and biomimetic chromatography were applied to characterize the lipophilicity of sulfonamide derivatives with proven anticancer activities against human colon cancer. Chromatographically determined lipophilicity parameters were compared with obtained logP, employing various computational approaches. Similarities and dissimilarities between experimental and computational logP were studied using principal component analysis, cluster analysis, and the sum of ranking differences. Furthermore, quantitative structure–retention relationship modeling was applied to understand the influences of sulfonamide's molecular properties on lipophilicity and affinity to phospholipids. [ABSTRACT FROM AUTHOR]

Copyright of Adiyaman University Journal of Science & Technology / Adıyaman Üniversitesi Fen Bilimleri Dergisi is the property of Adiyaman University, Institute of Science / Adiyaman Universitesi Fen Bilimleri Enstitusu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7 – 9, 11 – 13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure–activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays. [ABSTRACT FROM AUTHOR]

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

Alzheimer is a prolonged neurodegenerative disease which degenerate the brain cells and particularly affects the person ability to function independently. Despite of dynamic research, there is no proper treatment but can limit their persistent effect in early stages. In search of more potent drug for Alzheimer treatment, we have synthesized indole-based sulfonamide derivatives (1–17). All analogs were screened to find out lead candidate against acetylcholinesterase enzyme under positive control of donepezil as standard drug. Herein this study, analogs 1–4, 6–9, and 13–15 showed potent inhibition while kinetic studies further confirmed their mode of inhibition. All the synthesized analogs were characterized through HR-EI-MS, 1H NMR and 13C NMR spectroscopic techniques.

• A new sulfonamide derivative and its Cu(II) complex were produced and characterized. • CHNS, FT-IR, NMR, LC-MS, conductivity, magnetic susceptibility and TGA analysis were done. • Various quantum chemical calculations were performed for the produced structures. • ADME, druglikeness and toxicity predictions were also determined for the compounds. Sulfonamide and its derivatives are important antibacterial and antimicrobial agents in treating infections. In this study, a new sulfonamide derivative and its Cu(II) complex were produced and characterized due to their biological and medical importance. The structures of the produced compounds were elucidated using CHNS elemental analysis, spectroscopic techniques (FT-IR, NMR), and quantum chemical calculations. Vibrational modes, molecular electrostatic potential maps, and HOMO-LUMO analyses were performed for each compound. Important reactive descriptors of compounds were calculated, and the effects of solvent media on these parameters were revealed. In addition, drug-likeness, ADME, toxicity, molecular docking, and activity results of carbonic anhydrase, important parameters for biological and medical investigations, were determined. [Display omitted] [ABSTRACT FROM AUTHOR]

Sulfonamides are a classic group of chemotherapeutic drugs with a broad spectrum of pharmacological action, including anticancer activity. In this work, reversed-phase high-performance liquid chromatography and biomimetic chromatography were applied to characterize the lipophilicity of sulfonamide derivatives with proven anticancer activities against human colon cancer. Chromatographically determined lipophilicity parameters were compared with obtained logP, employing various computational approaches. Similarities and dissimilarities between experimental and computational logP were studied using principal component analysis, cluster analysis, and the sum of ranking differences. Furthermore, quantitative structure–retention relationship modeling was applied to understand the influences of sulfonamide’s molecular properties on lipophilicity and affinity to phospholipids.

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

In the planned research work, the nucleophilic substitution reaction of 1-[(E)-3-phenyl-2-propenyl]piperazine (1) was carried out with different sulfonyl chlorides (2a-g) at pH 9-10 to synthesize its different N-sulfonated derivatives (3a-g). The structures of the synthesized compounds were characterized by their proton-nuclear magnetic resonance (1HNMR), carbon-nuclear magnetic resonance (13C-NMR) and Infra Red (IR) spectral data, along with CHN analysis. The inhibition potential of the synthesized molecules was ascertained against two bacterial pathogenic strains i.e. Bacillus subtilis and Escherichia coli. It was inferred from the results that some of the compounds were very suitable inhibitors of these bacterial strains. Moreover, their cytotoxicity was also profiled and it was outcome that most of these molecules possessed moderate cytotoxicity. [ABSTRACT FROM AUTHOR]

The discovery of acetylcholinesterase inhibitors is important for the treatment of Alzheimer's disease (AD), known as the most common type of dementia. Due to the side effects of commonly used acetylcholinesterase inhibitors, studies for the detection of new inhibitors are increasing day by day. In this study, we investigated the effects of some sulfonamide derivatives (S1–S4 and S1i–S4i) on AChE enzymes. The best pose of the active compounds to understand the mechanism of possible inhibition in interaction of enzyme-sulfonamide derivative were performed docking studies after in vitro experimental results. ADME-related physicochemical and pharmacokinetic properties of the synthesized 4-aminobenzenesulfonamide derivatives were the compatibility with Lipinski's rule of five. We found that the synthesized derivatives of sulfonamides show potential inhibitor properties for AChE with Ki constants in the range of 2.54 ± 0.22–299.60 ± 8.73 µM. The derivatives of sulfonamides exhibited different inhibition type. We determined that the derivatives (S1, S1i, S3, and S3i) showed a competitive inhibition effect, whereas others (S2, S2i, S4, and S4i) showed mixed-type inhibition. As a result, the sulfonamide derivatives can be used as an alternative acetylcholinesterase inhibitor due to this effect. Inhibitors with fewer side effects, are thought to be important in the treatment of AD. [ABSTRACT FROM AUTHOR]

In this paper, two new Schiff bases (L1 and L2) derived from substituted salicylaldehyde and sulfamethoxazole/sulfisoxazole were synthesized. The synthesized structures were elucidated by experimental spectroscopic methods such as FT-IR, 1H-13C NMR, 1H, and 13C shielding tensors, and elemental analysis. The theoretical vibrational modes and nonlinear optical (NLO) properties have been computed by DFT/B3LYP/6-311G(d,p) method. Theoretical 1H and 13C shielding tensors were calculated with GIAO methods in CDCl3 with same level of theory. The results have shown that there is perfect harmony between the calculated parameters and recorded experimental data. The first order hyperpolarizabilities of the new synthesized compounds are 201.79 and 113.14 times larger than that of urea (0.3728 × 10–30 esu), respectively. According to evaluated results, the L1 and L2 present large nonlinear optical activity and are candidate molecules for nonlinear optical applications. [ABSTRACT FROM AUTHOR]

Facile synthetic procedures and broad spectrum of biological activities are special attributes of sulfonamides. Sulfonamide derivatives have demonstrated potential as a class of compounds for the treatment of Alzheimer's disease (AD). Recent sulfonamide derivatives have been reported as prospective anti-AD agents, with a focus on analogues that significantly inhibit the function of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and exhibit remarkable antioxidant and anti-inflammatory properties, all of which are critical for the treatment of AD. Sulfonamide- mediated activation of nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of the endogenous antioxidant response, has also been suggested as a potential therapeutic approach in AD. Additionally, it has been discovered that a number of sulfonamide derivatives show selectivity for the β- and γ-secretase enzymes and a significant reduction of amyloid B (Aβ) aggregation, which have been implicated in AD. The comparative molecular docking of benzenesulfonamide and donepezil, an AD reference drug showed comparable anti-AD activities. These suggest that sulfonamide derivatives may represent a new class of drugs for the treatment of AD. Thus, the current review will focus on recent studies on the chemical synthesis and evaluation of the anti-AD properties, molecular docking, pharmacological profile, and structure-activity relationship (SAR) of sulfonamide derivatives, as well as their potential anti-AD mechanisms of action. This paper offers a thorough assessment of the state of the art in this field of study and emphasizes the potential of sulfonamide derivatives synthesized during the 2012-2023 period as a new class of compounds for the treatment of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of new urea/thiourea derivatives 3a–j were synthesized by simple addition reaction of functionalized phenyl isocyanates/isothiocyanates 2a–j with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine (imatinib intermediate) (1) in the presence of 1,4-dimethyl piperazine (DMPZ) as a base, and another series of new sulfonamide/carbamate derivatives 5a–k were synthesized by reacting 1 with various substituted aromatic sulfonyl chlorides 4a–f and aromatic/aliphatic chloroformates 4g–k in the presence of DMPZ as a base. The title compounds 3a–j and 5a–k were characterized by IR, 1H, 13C NMR and mass spectral data. Antimicrobial, antioxidant and in silico molecular docking studies were made against aromatase. [ABSTRACT FROM AUTHOR]

To explore small molecules with ethylene-like biological activity, we conducted a triple response-based assay system for chemical library screening. Among 9600 compounds, we found N-[(1,3,5-trimethyl-1H-pyrazol-4-yl)methyl]-N-methyl-2-naphthalenesulfonamide (EH-1) displayed promising biological activity on inducing a triple response in Arabidopsis seedlings. Chemical synthesis and structure-activity relationship (SAR) analysis of EH-1 analogues with different substitution patterns on the phenyl ring structure of the sulfonamide group indicated that 3,4-dichloro-N-methyl-N-(1,3,5-trimethyl-1H-pyrazol-4-yl-methyl)benzenesulfonamide (8) exhibits the most potent biological activity. To determine the mechanism of action, we conducted RNA sequencing (RNA-Seq) analysis of the effect of EH-1 and 1-aminocyclopropane-1-carboxylate (ACC), the precursor of ethylene biosynthesis, following the quantitative real-time polymerase chain reaction (RT-PCR) confirmation. Data obtained from RNA-Seq analysis indicated that EH-1 and ACC significantly induced the expression of 39 and 48 genes, respectively (above 20 fold of control), among which five genes are up-regulated by EH-1 as well as by ACC. We also found 67 and 32 genes that are significantly down-regulated, respectively, among which seven genes are in common. For quantitative RT-PCR analysis. 12 up-regulated genes were selected from the data obtained from RNA-Seq analysis. We found a good correlation of quantitative RT-PCR analysis and RNA-Seq analysis. Based on these results, we conclude that the action mechanism of EH-1 on inducing triple response in Arabidopsis is different from that of ACC. [ABSTRACT FROM AUTHOR]

Chitosan (Ch), a linear cationic biopolymer, has broad medical applications. In this paper, new sustainable hydrogels (Ch-3, Ch-5 a , Ch-5 b) based on chitosan/sulfonamide derivatives 2-chloro-N-(4-sulfamoylphenethyl) acetamide (3) and/or 5-[(4-sulfamoylphenethyl) carbamoyl] isobenzofuran-1,3-dione (5) were prepared. Hydrogels (Ch-3, Ch-5 a , Ch-5 b) were loaded (Au, Ag, ZnO) NPs to form its nanocomposites to improve the antimicrobial efficacy of chitosan. The structures of hydrogels and its nanocomposites were characterized using different tools. All hydrogels displayed irregular surface morphology in SEM, however hydrogel (Ch-5 a) revealed the highest crystallinity. The highest thermal stability was shown by hydrogel (Ch-5 b) compared to chitosan. The nanocomposites represented nanoparticle sizes <100 nm. Antimicrobial activity was assayed for hydrogels using disc diffusion method exhibited great inhibition growth of bacteria compared to chitosan against S. aureus , B. subtilis and S. epidermidis as Gram-positive, E. coli , Proteus, and K. pneumonia as Gram-negative and antifungal activity against Aspergillus Niger and Candida. Hydrogel (Ch-5 b) and nanocomposite hydrogel (Ch-3/Ag NPs) showed higher colony forming unit (CFU) and reduction% against S. aureus and E. coli reaching 97.96 % and 89.50 % respectively in comparison with 74.56 % and 40.30 % for chitosan respectively. Overall, fabricated hydrogels and its nanocomposites enhanced the biological activity of chitosan and it can be potential candidates as antimicrobial drugs. [Display omitted] • New hydrogels Ch-3, Ch-5 a , Ch-5 b based on chitosan and sulfonamides were prepared. • Nanocomposites hydrogels-based on Au, Ag, ZnO NPs were formulated. • Hydrogel Ch-5 a showed the highest inhibition zone diameter (19 mm) against S. aureus. • Hydrogel Ch-5 b revealed the highest inhibition zone diameter (16 mm) toward Candida. • Hydrogel Ch-5 b displayed the highest reduction% reaching 97.96 % toward S. aureus. [ABSTRACT FROM AUTHOR]

[Display omitted] Fourteen new compounds bearing sulfonamide groups that target EGFRT790M/L858R mutations and ALK rearrangement were synthesized and evaluated as dual-target tumor inhibitors. The study on the anti-proliferation activity on cancer cells showed that the sulfonamide derivative with pyrimidine nucleus had much better activities compared with those with quinazoline nucleus. Among them, compound 19e exhibited excellent activity against H1975 cancer cell lines (EGFRT790M/L858R high express) and H2228 cells (ALK rearrangement) with the IC 50 values of 0.0215 μM and 0.011 μM, respectively. The ALK and EGFR kinase inhibition assays also provided similar results. Genotype selectivity of EGFR on kinase and cell level, cytotoxicity towards human normal cell lines and cell morphology assay implied that 19e had acceptable selectivity and low toxicity. In addition, the inhibitory activity of 19e on H1975 and H2228 cells cloning and its apoptosis-inducing effect on the two cell lines were studied, and its inhibitory effect on the invasion and migration of tumor cells were also investigated. All the results show that 19e is worthy of further study. [ABSTRACT FROM AUTHOR]

A simple and convenient method for the synthesis of biologically active sulfonamide derivatives was achieved. All the title compounds were characterized by spectral and elemental analysis. They were further screened in vitro for their abilities towards antibacterial, antifungal and antioxidant activities. The compoundN,N'-(3,3′-dimethoxybiphenyl-4,4′-diyl)bis(4-fluorobenzenesulfonamide) (5b) andN-(3-(9H-carbazol-4-yloxy)-2-hydroxypropyl)-4-fluoro-N-isopropylbenzenesulfonamide (5e) exhibited good activity when compared to the standard bactericide, Chloramphenicol and fungicide, Ketoconazole respectively. The compounds (2S)-N-((2S,4S)-5-(4-Chloro-phenylsulfonamido)-4-hydroxy-1, 6-diphenylhexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrim-idin-1(2H)-yl)butan-amide (4f) and (2S)-N-((2S,4S)-5-(4-fluorophenylsulfonamido)-4-hydroxy-1,6-diphenyl-hexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)bu-tana-mide (5f) exhibited good antioxidant activity when compared with standard antioxidant, Ascorbic acid. [ABSTRACT FROM AUTHOR]

In this study, several sulfonamide derivatives, 4-(2-methylacetylamino)benzenesulfonamides were synthesized. Chemical structures of the derivatives were characterized by 1 H NMR, 13 C NMR, LC–MS–MS, UV–Vis, FTIR, photoluminescence and elemental analysis. Sulfanilamide was reacted with 2-bromopropionyl bromide, in the presence of pyridine, to form bromo-substituted sulfonamide key intermediates, which were subsequently treated with secondary amines to obtain novel sulfonamide derivatives. All the synthesized compounds were evaluated for in vitro antimicrobial activities and cytotoxicity. Increases in ring size, and rings bearing a nitrogen heteroatom led to improvements in antimicrobial activities. As the presence of CA IX and CA XII enzymes have been implicated in some cancerous tumors, the studies presented herein focuses on targeting these enzymes. It was found that the synthesized derivatives had in vitro anti-cancer properties, where compounds ( 3 – 6 ) were found to be active against all cancerous cells, and no cytotoxic effects on normal cells were observed. [ABSTRACT FROM AUTHOR]

The synthesis of a homologous series of alanine-based surfactants, namely sodium salts of n-alkanesulfonamido-2-propanoic acids in which n-alkane is n-dodecane, n-tetradecane, n-hexadecane, and n-octadecane having the formula RSONHCH (CH)COONa, is described. The starting materials used were a mixture of secondary positional isomers of n-alkanesulfonyl chlorides obtained by photosulfochlorination reaction using sulfuryl chloride and a catalyst. Surface properties of the aqueous solutions of the synthesized surfactants, including the critical micelle concentration and minimal surface tension δ, were determined using surface tension measurements at 25 °C. The surface excess Γ and minimum area per molecule ( A ) where calculated using the Gibbs equation. The foaming power was also determined by the Bartsh method, and the R parameter was calculated to estimate the stability of the foam formed. The results obtained were compared to those of a commercial surfactant, sodium dodecylsulfate, and a series of synthesized glycine-based surfactants. The results obtained clearly show that the alanine-based surfactants possess good surface properties. The investigations highlight the influence on the surface properties of the addition of a methyl group in the hydrophilic part. [ABSTRACT FROM AUTHOR]

Starting from 4-chlorobenzoic acid, 10 new 5-(4-chlorophenyl)-N-substituted-N-1,3,4-thiadiazole-2-sulfonamide derivatives were synthesized in six-steps. Esterification of 4-chlorobenzoic acid with methanol and subsequent hydrazination, salt formation and cyclization afforded 5-(4-chlorophen-yl)-1,3,4-thiadiazole-2-thiol (5). Conversion of this intermediate into sulfonyl chloride 6, followed by nucleophilic attack of the amines gave the title sulfonamides 7a-7j whose structures were confirmed by NMR, IR and elemental analysis. The bioassay tests showed that compounds 7b and 7i possessed certain anti-tobacco mosaic virus activity.

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase  H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the  H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC 50 ) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC 50 =18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives. [ABSTRACT FROM AUTHOR]

NLRP3 inflammasome dysregulation has been observed in many human diseases including neurodegenerative disorders. Thus, development of small molecule inhibitors targeting this protein complex represents a promising strategy to achieve disease intervention. In our continuing efforts to develop NLRP3 inhibitors, a recently identified lead inhibitor, YQ128 , was further modified and optimized. The structure-activity relationship studies of this lead compound suggested its flexibility for structural modifications while the sulfonamide and benzyl moiety demonstrated being important for selectivity. Additionally, the systematic SAR studies also provided insights for designing NLRC4 and AIM2 inflammasome inhibitors. A new lead inhibitor, 19 , was identified with improved potency (IC 50 : 0.12 ± 0.01 μM) and binding affinity (K D : 84 nM). Further characterization of this lead compound using wild type and nlrp3−/− mice confirmed its in vivo selective target engagement. PET studies using a radiotracer based on the structure of 19 also demonstrated its improved brain penetration compared to previous lead compounds. These results strongly encourage further testing of 19 in disease models. [Display omitted] • Systematic SAR studies were performed based on the sulfonamide scaffold of YQ128. • Compound 19 demonstrated as an NSI with an IC 50 of 0.12 μM and K D of 84 nM. • Studies of 19 in mice demonstrated its in vivo target engagement. • PET/CT studies of [18F] 19 demonstrated rapid brain uptake and penetration. [ABSTRACT FROM AUTHOR]

New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure–activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays. Among the compounds, compound 3i exhibited the most potent inhibitory activity with IC 50 values of 0.21 μM inhibiting MMP-2 and 1.87 μM inhibiting MMP-9, comparable to the control positive compound CMT-1 (1.26 μM, 2.52 μM). Docking simulation was performed to position compound 3i into the MMP-2 active site to determine the probable binding pose. Docking simulation was further performed to position compound 3i into the MMP-2 active site to determine the probable binding model the 3D-QSAR models were built for reasonable design of MMP-2/MMP-9 inhibitors at present and in future. [ABSTRACT FROM AUTHOR]

Herein, the compounds bearing sulfonamide fragment such as N-(2-amino-5-benzoylphenyl)-4-nitrobenzene sulfonamide hydrochloride ( 1), N-(quinolin-8-yl)-4-nitro-benzenesulfonamide hydrochloride ( 2), N-(pyridine-2-ylmethyl)-4-nitro-benzenesulfonamide hydrochloride ( 3) were synthesized by the reaction of 3,4-diaminobenzophenone, 8-aminoquinoline or 2-picoylamine and 4-nitrobenzensulfonyl chloride, respectively. The structures of the newly synthesized compounds were elucidated on the basis of elemental and spectral analyses. All the prepared compounds were evaluated for their in vitro anti-cancer activity against various cancer cell lines and to explore the underlying molecular mechanisms involved in this process. In vitro cytotoxic activities of the compounds were screened against human hepatocellular (HepG2), breast (MCF-7) and colon (Colo-205) cancer cell lines by MTT assay, mRNA expression of genes with qPCR and phosphorylation of p38 and ERK1/2 with Western blot. Tested compounds could significantly reduce cell proliferation and induced mRNA expression of pro-apoptotic genes; caspase 3, caspase 8 and caspase 9. Activation of these apoptotic genes probably is mediated by activation of p38. [ABSTRACT FROM AUTHOR]

Three sulfonamide derivatives (SAD) were first synthesized from p-hydroxybenzoic acid and sulfonamides (sulfadimidine, sulfamethoxazole and sulfachloropyridazine sodium) and were characterized by elemental analysis, 1H NMR and MS. The interaction between bovine serum albumin (BSA) and SAD was studied using UV/vis absorption spectroscopy, fluorescence spectroscopy, time-resolved fluorescence spectroscopy and circular dichroism spectra under imitated physiological conditions. The experimental results indicated that SAD effectively quenched the intrinsic fluorescence of BSA via a static quenching process. The thermodynamic parameters showed that hydrogen bonding and van der Waal's forces were the predominant intermolecular forces between BSA and two SADs [4-((4-( N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate and 4-((4-( N-(5-methylisoxazol-3-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate], but hydrophobic forces played a major role in the binding process of BSA and 4-((4-( N-(6-chloropyridazin-3-yl)sulfamoyl)phenyl) carbamoyl)phenyl acetate. In addition, the effect of SAD on the conformation of BSA was investigated using synchronous fluorescence spectroscopy and circular dichroism spectra. Molecular modeling results showed that SAD was situated in subdomain IIA of BSA. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The complexes formed between six original chiral diaryl-pyrazole sulfonamide derivatives, displaying poor solubility, and various CDs (native α-, β- and γ-CDs, hydroxypropylated HP-β-CD, methylated Me-β-CD or amino NH 2 -β-CD) were studied by 1D and 2D 1 H NMR at physiological pH in order to determine their apparent binding constant, stoichiometry and structure of the supramolecular assembly. For some complexes, the spectra obtained for free racemic compound and for racemic compound in presence of CD indicate a splitting of signal(s). Additional experiments with pure enantiomer and enriched enantiomer allow us to attribute this behavior to chiral discrimination. The complexing ability of the native β-CD towards our compounds appears the most promising since binding values around 7 × 10 2 M −1 are obtained. The two-dimensional ROESY ( 1 H– 1 H) experiments prove the inclusion of the aliphatic part of the compound in the CD cavity. It is noteworthy that this inclusion occurs via the smaller opening of the cavity. [ABSTRACT FROM AUTHOR]

An efficient and simple microwave assisted synthesis of sulfonamide derivatives incorporating the pyridazine moiety has been developed. These sulfonamides were used for the preparation of new heterocyclic compounds via reaction with different reagents using a microwave irradiation technique. The structures of the newly synthesized compounds were confirmed on the basis of FTIR, 1H and 13C-NMR, mass spectral techniques and elemental analyses. Some of the new synthesized compounds were assayed for their in vitro antibacterial activity against Gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, Gram-negative bacteria, Escherichia coli and Klebsiella pneumonia and antifungal activity against Aspergillus fumigatus and Candida albicans. Most of the new compounds showed significant antibacterial and antifungal activity. [ABSTRACT FROM AUTHOR]

Retinoic acid receptor related orphan receptor γt (RORγt), identified as the essential functional regulator of IL-17 producing Th17 cells, is an attractive drug target for treating autoimmune diseases. Starting from the reported GSK2981278 (Phase II), we structurally modified and synthesized a series of 2 H -chromone-4-one based sulfonamide derivatives as novel RORγt inverse agonists, which significantly improved their human metabolic stabilities while maintaining a potent RORγt inverse agonist profile. Efforts in reducing the lipophilicity and improving the LLE values led to the discovery of c9 , which demonstrated potent RORγt inverse agonistic activity and consistent metabolic stability. During in vivo studies, oral administration of compound c9 exhibited a robust and dose-dependent inhibition of IL-17A cytokine expression and significantly lessened the skin inflammatory symptoms in the mouse imiquimod-induced skin inflammation model. Docking analysis of the binding mode revealed that c9 can suitably occupy the active pocket, and the introduction of the morpholine pyridine group can interact with Leu396, His479, and Cys393. Thus, compound c9 was selected as a preclinical compound for treating Th17-driven autoimmune diseases. [Display omitted] • 45 RORγt inverse agonists were synthesized and evaluated the biological activities. • c9 has better pharmacokinetic profile than GSK2981278. • c9 significantly lessened the skin inflammatory symptoms. [ABSTRACT FROM AUTHOR]

Abstract: A series of thiazolone derivatives was designed and synthesized as potential HCV NS5B allosteric polymerase inhibitors at the allosteric site thumb II. Their antiviral activity was evaluated and molecular modeling was utilized to give further envision on their probable binding modes in the allosteric binding site. Among the tested molecules, compound 9b displayed sub-micromolar inhibitory activity with an EC50 of 0.79 μM indicating excellent potency profile. It also showed good safety profile (CC50 ≥ 75 μM and SI ≥ 94.3). [Copyright &y& Elsevier]

Abstract: A series of sulfonamides containing coumarin moieties had been prepared that showed a very interesting profile for the inhibition of two human carbonic anhydrase inhibitors. These compounds were evaluated for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA II and the tumor-associated isozyme hCA IX. The most potent inhibitor against hCA II and IX were compounds 5d (IC50 = 23 nM) and 5l (IC50 = 24 nM), respectively. These sulfonamides containing coumarin moieties may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly. Eighteen compounds were scrutinized by CoMFA and CoMSIA techniques of 3D quantitative structure–activity relationship. Nine of the compounds were evaluated for cytotoxicity against human macrophage. [Copyright &y& Elsevier]

Synthesis and antibacterial activity of some novel biologically active sulfonamide derivatives at C-8 alkyl chain of anacardic acid ( 7a-7l), prepared from commercially available anacardic acid mixture ( 1a-d). These compounds were tested for Gram positive and Gram negative bacterial cultures; most of the compounds showed higher antibacterial activity compared with standard drug ampicillin. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: The work presents synthesis and characterization of novel sulfadimethoxine and sulfabenzamide azo derivatives as well as the kinetic study of their trans–cis–trans isomerization. Spectral properties and kinetic constants were determined for the chromophores dispersed in poly(methyl methacrylate-co-butyl methacrylate) deposited on glass substrates in form of transparent, thin films. The maximum absorption bands were observed within wavelength in range of 446–457 nm for N-disubstituted aminoazobenzene derivatives and 361–362 nm for phenolic chromophores. For the phenolic azo derivatives of sulfadimethoxine and sulfabenzamide the photoisomerization induced with UV light followed the first order kinetics, while for other compounds the process combined of two parallel reactions with different rate constants was observed. The rate constants of thermal relaxation in the dark were usually few times smaller than those determined for photoinduced trans–cis isomerization. The change of real part of refractive index upon illumination determined by ellipsometry was within the range of 0.0043–0.0138. [Copyright &y& Elsevier]

Abstract: New series of sulfonamide derivatives of [1,3,4]thiadiazolo[3,2-a]pyrimidine were synthesized and investigated as antitumor agents. Some of the newly prepared compounds were tested for their in vitro and in vivo antitumor activities. Preliminary biological studies revealed that compounds 4c, 4f, and 4j exhibited the highest affinity to DNA, while compounds 4h,i, 6a–c, 8 and 12–14 exhibited moderate activity. Also, compounds 4j, 4f and 4c showed the highest percentage increase in lifespan of mice inoculated with Ehrlich ascites cells over 5-flurouracil (positive control). The detailed synthesis, spectroscopic and biological data are reported. [Copyright &y& Elsevier]

Starting from 4-chlorobenzoic acid, 10 new 5-(4-chlorophenyl)-N-substituted-N- 1,3,4-thiadiazole-2-sulfonamide derivatives were synthesized in six-steps. Esterification of 4-chlorobenzoic acid with methanol and subsequent hydrazination, salt formation and cyclization afforded 5-(4-chlorophen-yl)-1,3,4-thiadiazole-2-thiol (5). Conversion of this intermediate into sulfonyl chloride 6, followed by nucleophilic attack of the amines gave the title sulfonamides 7a-7j whose structures were confirmed by NMR, IR and elemental analysis. The bioassay tests showed that compounds 7b and 7i possessed certain antitobacco mosaic virus activity. [ABSTRACT FROM AUTHOR]

Abstract: Three dinuclear and one mononuclear copper(II)-1,10-phenanthroline ternary complexes, [Cu(L1)(phen)(OH)]2 (1), [Cu(L2)(phen)(OH)]2·3H2O (2), [Cu(L3)(phen)(OH)]2 (3) and [Cu(L4)2(phen)(H2O)] (4), with thiadiazole sulfonamide derivative ligands: HL1 (N-(5-ethyl-1,3,4-thiadiazol-2-yl)naphthalene-1-sulfonamide), HL2 (N-(5-ethylthio)-1,3,4-thiadiazol-2-yl)-4-methylbenzenesulfonamide), HL3 (N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide) and HL4 (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-4-methylbenzenesulfonamide) have been synthesized and characterized. In the four complexes each copper atom is five-coordinated. The structure of complexes 1, 2 and 3 consists of a dimeric unit with a C2 symmetry axis, where both coppers are bridged by two hydroxo anions. Magnetic measurements show that the dimer complexes are ferromagnetic according to the Cu–O–Cu angles. Cleavage experiments using pUC18 plasmid DNA in the presence of H2O2/ascorbic acid as an activating agent show that the title complexes are potent artificial chemical nucleases, the order of efficiency being 3 > 2 ∼ 1 > 4. Control cleavage experiments indicated that the dimer complexes are stronger artificial nucleases than the [Cu(phen)2]2+ complex under the same experimental conditions, while the monomer 4 has a lower nuclease activity than the [Cu(phen)2]2+ complex. The inhibition of the cleavage process in the presence of reactive oxygen intermediate scavengers suggests that the hydroxyl radical and the superoxide anion are reactive species for the breakage of the DNA strands. [Copyright &y& Elsevier]