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Keywords = benzenesulfonamides

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31 pages, 19845 KiB  
Article
In Silico Approaches for the Discovery of Novel Pyrazoline Benzenesulfonamide Derivatives as Anti-Breast Cancer Agents Against Estrogen Receptor Alpha (ERα)
by Dadang Muhammad Hasyim, Ida Musfiroh, Rudi Hendra, Taufik Muhammad Fakih, Nur Kusaira Khairul Ikram and Muchtaridi Muchtaridi
Appl. Sci. 2025, 15(15), 8444; https://doi.org/10.3390/app15158444 - 30 Jul 2025
Viewed by 398
Abstract
Estrogen receptor alpha (ERα) plays a vital role in the development and progression of breast cancer by regulating the expression of genes associated with cell proliferation in breast tissue. ERα inhibition is a key strategy in the prevention and treatment of breast cancer. [...] Read more.
Estrogen receptor alpha (ERα) plays a vital role in the development and progression of breast cancer by regulating the expression of genes associated with cell proliferation in breast tissue. ERα inhibition is a key strategy in the prevention and treatment of breast cancer. Previous research modified chalcone compounds into pyrazoline benzenesulfonamide derivatives (Modifina) which show activity as an ERα inhibitor. This study aimed to design novel pyrazoline benzenesulfonamide derivatives (PBDs) as ERα antagonists using in silico approaches. Structure-based and ligand-based drug design approaches were used to create drug target molecules. A total of forty-five target molecules were initially designed and screened for drug likeness (Lipinski’s rule of five), cytotoxicity, pharmacokinetics and toxicity using a web-based prediction tools. Promising candidates were subjected to molecular docking using AutoDock 4.2.6 to evaluate their binding interaction with ERα, followed by molecular dynamics simulations using AMBER20 to assess complex stability. A pharmacophore model was also generated using LigandScout 4.4.3 Advanced. The molecular docking results identified PBD-17 and PBD-20 as the most promising compounds, with binding free energies (ΔG) of −11.21 kcal/mol and −11.15 kcal/mol, respectively. Both formed hydrogen bonds with key ERα residues ARG394, GLU353, and LEU387. MM-PBSA further supported these findings, with binding energies of −58.23 kJ/mol for PDB-17 and −139.46 kJ/mol for PDB-20, compared to −145.31 kJ/mol, for the reference compound, 4-OHT. Although slightly less favorable than 4-OHT, PBD-20 demonstrated a more stable interaction with ERα than PBD-17. Furthermore, pharmacophore screening showed that both PBD-17 and PBD-20 aligned well with the generated model, each achieving a match score of 45.20. These findings suggest that PBD-17 and PBD-20 are promising lead compounds for the development of a potent ERα inhibitor in breast cancer therapy. Full article
(This article belongs to the Special Issue Drug Discovery and Delivery in Medicinal Chemistry)
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14 pages, 2797 KiB  
Article
Homo- Versus Hetero- [2+2+2] Rhodium-Catalyzed Cycloaddition: Effect of a Self-Assembled Capsule on the Catalytic Outcome
by Maxime Steinmetz and David Sémeril
Molecules 2025, 30(14), 3052; https://doi.org/10.3390/molecules30143052 - 21 Jul 2025
Viewed by 259
Abstract
The cationic chloro-P-{[4-(diphenylphosphanyl)phenyl]-N,N-dimethylmethanammonio(norbornadiene)rhodium(I) complex was encapsulated inside a self-assembled hexameric capsule. This capsule was obtained through a reaction involving 2,8,14,20-tetra-undecyl-resorcin[4]arene and water in chloroform. The formation of an inclusion complex was deduced from a combination of spectral [...] Read more.
The cationic chloro-P-{[4-(diphenylphosphanyl)phenyl]-N,N-dimethylmethanammonio(norbornadiene)rhodium(I) complex was encapsulated inside a self-assembled hexameric capsule. This capsule was obtained through a reaction involving 2,8,14,20-tetra-undecyl-resorcin[4]arene and water in chloroform. The formation of an inclusion complex was deduced from a combination of spectral measurements (UV-visible spectroscopy, 1H, 31P{1H} NMR and DOSY). The rhodium complex was evaluated in the [2+2+2] cycloaddition between N,N-dipropargyl-p-toluenesulfonamide and arylacetylene derivatives. In the presence of two equivalents of arylacetylenes in water-saturated chloroform at 60 °C for 24 h, the 4-methyl-N-(prop-2-yn-1-yl)-N-((2-tosylisoindolin-5-yl)methyl)benzenesulfonamide, the homocycloaddition product of 1,6-diyne is predominantly formed. In the presence of the supramolecular capsule, a selectivity inversion in favor of 5-aryl-2-tosylisoindoline is observed, with heterocycloaddition products formed in proportions between 53 and 69%. Full article
(This article belongs to the Section Organometallic Chemistry)
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28 pages, 5716 KiB  
Article
Novel Benzenesulfonamide Derivatives of 5′-Aminospirotriazolotriazine Exhibit Anti-Inflammatory Activity by Suppressing Pro-Inflammatory Mediators: In Vitro and In Vivo Evaluation Using a Rat Model of Carrageenan-Induced Paw Edema
by Amany M. Hamed, Souhaila S. Enaili, Walaa I. Mohammed, Azza M. A. Abouelella, Zeyad Elsayed Eldeeb Mohana, Dina M. Monir, Safaa S. Soliman, Elsayed Eldeeb Mehana Hamouda, Hytham Mahmoud Abd Elatif and Ahmed M. El-Saghier
Biomedicines 2025, 13(7), 1732; https://doi.org/10.3390/biomedicines13071732 - 15 Jul 2025
Viewed by 853
Abstract
Background/Objectives: Inflammation is a crucial and complex mechanism that protects the body against infections. In our study, we propose to provide scientific evidence for the anti-inflammatory properties of 1,3,5-triazine derivatives. Methods: Initially, we ensured the safety of the three synthesized derivatives [...] Read more.
Background/Objectives: Inflammation is a crucial and complex mechanism that protects the body against infections. In our study, we propose to provide scientific evidence for the anti-inflammatory properties of 1,3,5-triazine derivatives. Methods: Initially, we ensured the safety of the three synthesized derivatives by administering graded doses of up to 2000 mg/kg intraperitoneally in Wistar rats. Thus, the three derivatives were considered generally safe. We also evaluated their ability to reduce carrageenan-induced rat paw edema. Results: Compounds 1, 2, and 3 demonstrated stronger anti-inflammatory activity than indomethacin (10 mg/kg), achieving maximum inhibition at the fourth hour with percentages of 96.31%, 72.08%, and 99.69%, respectively, at a dose of 200 mg/kg, compared to 57.66% for the standard drug. To explore the mechanism, levels of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6, CRP) and oxidative stress markers were measured in paw tissue. All three compounds significantly reduced these markers more effectively than indomethacin and enhanced antioxidant levels (SOD and GSH) beyond those achieved by the standard treatment. Additionally, the compounds reduced COX-1 and COX-2 levels to values comparable to those in the normal (non-inflamed) control group. Conclusions: Compounds 1, 2, and 3 at doses of 200 mg/kg significantly (p  < 0.05) inhibited the heat-induced hemolysis of red blood cell (RBC) membranes by 94.6%, 93.9%, and 95.2%, respectively, compared to 94.5% produced by indomethacin. Consequently, we concluded that 1,3,5-triazine derivatives are a safe antioxidant agent with significant anti-inflammatory activity. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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35 pages, 3911 KiB  
Article
Novel Derivatives of 3-Amino-4-hydroxy-benzenesulfonamide: Synthesis, Binding to Carbonic Anhydrases, and Activity in Cancer Cell 2D and 3D Cultures
by Valdas Vainauskas, Rugilė Norvaišaitė, Birutė Grybaitė, Rita Vaickelionienė, Alexey Smirnov, Tautvydas Kojis, Lina Baranauskiene, Elena Manakova, Saulius Gražulis, Asta Zubrienė, Daumantas Matulis, Vytautas Mickevičius and Vilma Petrikaitė
Int. J. Mol. Sci. 2025, 26(13), 6466; https://doi.org/10.3390/ijms26136466 - 4 Jul 2025
Viewed by 1067
Abstract
A series of novel derivatives of 3-amino-4-hydroxybenzenesulfonamide was synthesized. As the analyzed compounds possess a sulfonamide group, the affinity of these compounds for human carbonic anhydrases (CAs) was measured by fluorescent thermal shift assay, and compound selectivity for different isoenzymes was identified. The [...] Read more.
A series of novel derivatives of 3-amino-4-hydroxybenzenesulfonamide was synthesized. As the analyzed compounds possess a sulfonamide group, the affinity of these compounds for human carbonic anhydrases (CAs) was measured by fluorescent thermal shift assay, and compound selectivity for different isoenzymes was identified. The crystal structures of the complexes of compound 25 with CAI and CAII were determined. Additionally, the activity of compounds on the viability of three cancer cell lines—human glioblastoma U-87, triple-negative breast cancer MDA-MB-231, and prostate adenocarcinoma PPC-1—was established using the MTT assay and compared to CAIX-selective and non-selective comparative compounds U-104 and acetazolamide. The half-maximal concentration (EC50) was determined for the identified most active compounds, and their selectivity over fibroblasts was established. Compound 9 (inhibitor of multi-CAs) and compound 21 (not binding to CAs), considered the most promising candidates, were tested in cancer cell 3D cultures (cancer spheroids) by assessing their effect on spheroid growth and viability. Both compounds reduced the viability of spheroids from all cancer cell lines. U-87 and PPC-1 spheroids became looser in the presence of compound 9, while the growth of MDA-MB-231 spheroids was slower compared to the control. Compound 21 reduced the growth of U-87 and MDA-MB-231 3D cultures, with no significant effect on PPC-1 spheroids. Full article
(This article belongs to the Special Issue New Players in the Research of Oxidative Stress and Cancer)
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23 pages, 9420 KiB  
Article
Druggability Studies of Benzene Sulfonamide Substituted Diarylamide (E3) as a Novel Diuretic
by Hang Zhang, Shuyuan Wang, Nannan Li, Yue Xu, Zhizhen Huang, Yukun Zhang, Jing Li, Yinglin Zuo, Min Li, Runtao Li and Baoxue Yang
Biomedicines 2025, 13(4), 992; https://doi.org/10.3390/biomedicines13040992 - 18 Apr 2025
Cited by 1 | Viewed by 585
Abstract
Background/Objectives: Urea transporters (UTs) play an important role in the urine-concentrating mechanism and have been regarded as a novel drug target for developing salt-sparing diuretics. Our previous studies found that diarylamides 1H and 25a are specific UT inhibitors and have oral diuretic [...] Read more.
Background/Objectives: Urea transporters (UTs) play an important role in the urine-concentrating mechanism and have been regarded as a novel drug target for developing salt-sparing diuretics. Our previous studies found that diarylamides 1H and 25a are specific UT inhibitors and have oral diuretic activity. However, these compounds necessitate further optimization and comprehensive druggability studies. Methods: The optimal compound was identified through structural optimization. Experiments were conducted to investigate its UT inhibitory activity and evaluate its diuretic effect. Furthermore, disease models were utilized to assess the compound’s efficacy in treating hyponatremia. Pharmacokinetic studies were performed to examine its metabolic stability, and toxicity tests were conducted to evaluate its safety. Results: Based on the chemical structure of compound 25a, we synthesized a novel diarylamide compound, E3, by introducing a benzenesulfonamide group into its side chain. E3 exhibited dose-dependent inhibition of UT at the nanomolar level and demonstrated oral diuretic activity without causing electrolyte excretion disorders in both mice and rats. Experiments on UT-B−/− and UT-A1−/− mice indicated that E3 enhances the diuretic effect primarily by inhibiting UT-A1 more effectively than UT-B. Furthermore, E3 displayed good metabolic stability and favorable pharmacokinetic characteristics. E3 significantly ameliorated hyponatremia through diuresis in a rat model. Importantly, E3 did not induce acute oral toxicity, subacute oral toxicity, genotoxicity, or cardiotoxicity. Conclusions: Our study confirms that E3 exerts a diuretic effect by specifically inhibiting UTs and has good druggability, which offers potential for E3 to be developed into a new diuretic for the treatment of hyponatremia. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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5 pages, 932 KiB  
Short Note
N-(3-(tert-Butyl)-1-methyl-1H-pyrazol-5-yl)-4-methyl-N-tosylbenzenesulfonamide
by Diana Becerra and Juan-Carlos Castillo
Molbank 2025, 2025(2), M1992; https://doi.org/10.3390/M1992 - 15 Apr 2025
Viewed by 2195
Abstract
N-(3-(tert-Butyl)-1-methyl-1H-pyrazol-5-yl)-4-methyl-N-tosylbenzenesulfonamide was efficiently synthesized in good yield through a triethylamine-mediated sulfonamidation reaction of 3-(tert-butyl)-1-methyl-1H-pyrazol-5-amine with 4-methylbenzenesulfonyl chloride in acetonitrile at room temperature. The pyrazole-based benzenesulfonamide was fully characterized using FT-IR, NMR, and HMRS techniques. Full article
(This article belongs to the Collection Heterocycle Reactions)
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12 pages, 3221 KiB  
Article
Electron Beam Irradiation-Induced Degradation of Sulfadiazine in Aqueous Solutions
by Boris Tende Kengne, Shizong Wang, Yongxia Sun, Jianlong Wang and Sylwester Bulka
Water 2025, 17(7), 1077; https://doi.org/10.3390/w17071077 - 4 Apr 2025
Cited by 2 | Viewed by 575
Abstract
The degradation of sulfadiazine (4-amino-N-pyrimidin-2yl-benzenesulfonamide, SDZ), a widely used sulfonamide antibiotic, in aqueous solution under electron beam irradiation was investigated to explore its potential as an Advanced Oxidation Process for environmental remediation. This study evaluated the effects of irradiation dose, initial [...] Read more.
The degradation of sulfadiazine (4-amino-N-pyrimidin-2yl-benzenesulfonamide, SDZ), a widely used sulfonamide antibiotic, in aqueous solution under electron beam irradiation was investigated to explore its potential as an Advanced Oxidation Process for environmental remediation. This study evaluated the effects of irradiation dose, initial sulfadiazine concentration, and initial pH on the degradation efficiency. It was found at 0.5 kGy that the degradation efficiency decreased with increasing initial SDZ concentration, from 83.0% at 5 mg/L to 35.0% at 30 mg/L. The kinetic results showed a pseudo-first order model. The degradation efficiencies of 30 mg/L SDZ reached 80.8%, 75.3%, 69.5% and 69.8%, respectively, at pH 3.0, 6.3, 9.0, and 11.0 at 3.0 kGy, indicating the pH dependence to SDZ degradation under electron beam. The maximum removal efficiency was around 90% after UV analysis and 99% after HPLC analysis for 10mg/L SDZ at absorbed doses of 2–3 kGy and pH 6.3. Increasing the degradation efficiency of 10 mg/L SDZ from 0.5 kGy to 3.0 kGy showed the dose dependence on SDZ removal. Reactive species generated during irradiation, including hydroxyl radicals, hydrogen radicals, and solvated electrons, were identified as primary contributors to the degradation process. The effect of reactive species on the degradation of 10 mg/L SDZ was evaluated at variable doses, revealing the following trend: OH>H>eaq. Transformation products were characterized using high-performance liquid chromatography (HPLC) and mass spectrometry (MS), providing insights into the degradation pathway. The results demonstrate that electron beam irradiation is an effective and sustainable method for sulfadiazine removal in water treatment systems, offering an innovative approach to mitigating antibiotic pollution in aquatic environments. Full article
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12 pages, 1174 KiB  
Article
In Vitro Activity of the Triazinyl Diazepine Compound FTSD2 Against Drug-Resistant Mycobacterium tuberculosis Strains
by Carlos Aranaga, Ruben Varela, Aura Falco, Janny Villa, Leydi M. Moreno, Manuel Causse and Luis Martínez-Martínez
Pharmaceuticals 2025, 18(3), 360; https://doi.org/10.3390/ph18030360 - 2 Mar 2025
Viewed by 917
Abstract
Background/Objectives: Compounds derived from pyrimido-diazepine have shown selective inhibition of the susceptible Mycobacterium tuberculosis strain H37Rv. However, there is a need for studies that evaluate the activity of these compounds against multidrug-resistant strains and clinical isolates. This study aims to evaluate the antitubercular [...] Read more.
Background/Objectives: Compounds derived from pyrimido-diazepine have shown selective inhibition of the susceptible Mycobacterium tuberculosis strain H37Rv. However, there is a need for studies that evaluate the activity of these compounds against multidrug-resistant strains and clinical isolates. This study aims to evaluate the antitubercular potential of FTSD2 against drug-resistant strains of M. tuberculosis. Methods: The compound 4-(2,4-diamino-8-(4-methoxyphenyl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepin-6-yl)-N-(2-(4-(dimethylamino)-6-(4-fluorophenyl)amino-1,3,5-triazin-2-yl)amino)ethyl)benzenesulfonamide (FTSD2) was tested against drug-resistant M. tuberculosis strains at minimal inhibitory and bactericidal concentrations (MIC and MBC). Kill curve assays were performed to assess bactericidal activity, and cytotoxicity was evaluated in human monocyte-derived macrophages and the RAW 264.7 murine macrophage cell line. Intracellular death assays, specifically macrophage infection assays, were also conducted to evaluate the effect of FTSD2 on intracellular M. tuberculosis growth. Results: FTSD2 inhibited the growth of drug-resistant M. tuberculosis at MIC and MBC values between 0.5 and 1 mg/L. Kill curve assays demonstrated concentration-dependent bactericidal activity. No cytotoxicity was observed in macrophages at concentrations below 64 mg/L. Additionally, FTSD2 significantly suppressed intracellular M. tuberculosis growth after 192 h. FTSD2 did not inhibit the growth of nontuberculous mycobacteria, including M. avium, M. abscessus, M. fortuitum, M. chelonae, and M. smegmatis at 50 mg/L. Conclusions: FTSD2 exhibits strong potential as a leading compound for the development of new antitubercular drugs, with selective activity against M. tuberculosis and minimal cytotoxic effects on macrophages. Further studies are needed to explore its mechanisms of action and therapeutic potential. Full article
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12 pages, 3546 KiB  
Article
Antiviral Effect and Metabolic Regularity of a Phenylpropanoid- Based Compound as Potential Immunopotentiator
by Dawei Song, Xue Cai, Qianhao Shao, Xinhui Tong, Zhe Zhao, Lei Liu and Guanglu Liu
Fishes 2025, 10(2), 77; https://doi.org/10.3390/fishes10020077 - 15 Feb 2025
Viewed by 528
Abstract
Spring viremia of carp virus (SVCV) is a significant pathogen that has notably hindered the advancement of cyprinid aquaculture in recent years. Infections caused by SVCV are often associated with substantial economic losses due to the absence of effective treatment options. Previous reports [...] Read more.
Spring viremia of carp virus (SVCV) is a significant pathogen that has notably hindered the advancement of cyprinid aquaculture in recent years. Infections caused by SVCV are often associated with substantial economic losses due to the absence of effective treatment options. Previous reports indicated that N-(4-methyl-2-oxo-2H-chromen-7-yl) benzenesulfonamide (N6) exhibits inhibitory effects on SVCV proliferation. This study aims to comprehensively evaluate the anti-SVCV effects of N6 using healthy young carp as the experimental model. The research investigates the antiviral activity of this compound in vivo, the immune response of interferon (IFN)-related genes, its impact on the horizontal transmission of SVCV, and histopathological changes. The results indicate that N6 significantly inhibits SVCV infectivity and apoptosis in EPC cells in vitro. Furthermore, while N6 reduced horizontal transmission of SVCV in a static cohabitation challenge model, the N6-treated SVCV-infected group showed a nearly 3-fold decrease in viral load compared to the control group, it did not completely prevent transmission at established antiviral dosages. Histopathological analysis of the affected fish revealed that N6 effectively mitigated tissue damage induced by SVCV. Additionally, the up-regulation of six IFN-related genes suggests that N6 may indirectly activate IFNs to facilitate the clearance of SVCV in the kidney and spleen, as demonstrated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). These findings provide a foundation for further investigations into the mechanisms by which N6 acts against SVCV and may aid in the development of novel anti-SVCV therapeutics. Full article
(This article belongs to the Section Nutrition and Feeding)
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13 pages, 1428 KiB  
Article
Detailed Studies on the Methoxylation and Subsequent Dealkylation of N,N-Diethylbenzenesulfonamide Using a Tailor-Made Electrosynthetic Reactor
by Ernák F. Várda, Imre Gyűjtő, Ferenc Ender, Richárd Csekő, György T. Balogh and Balázs Volk
Molecules 2024, 29(23), 5496; https://doi.org/10.3390/molecules29235496 - 21 Nov 2024
Viewed by 1147
Abstract
Benzenesulfonamides are an outstandingly important family of compounds in organic and medicinal chemistry. Herein, we report detailed studies on the electrochemical mono- and dideethylation of model compound N,N-diethylbenzenesulfonamide. In this context, all parameters of the electrosynthesis were systematically investigated, with a special [...] Read more.
Benzenesulfonamides are an outstandingly important family of compounds in organic and medicinal chemistry. Herein, we report detailed studies on the electrochemical mono- and dideethylation of model compound N,N-diethylbenzenesulfonamide. In this context, all parameters of the electrosynthesis were systematically investigated, with a special emphasis on solvent screening and the effect of water on the outcome of the reaction. Beside a commercially available electrochemical reactor, a custom-made device has also successfully been designed and used in these transformations. Optimization of the reaction led to a green, scaled-up synthesis of the dealkylated products. Our experiments also render the synthesis and potential in situ use of the corresponding N-methoxyalkyl intermediate, a precursor of the reactive and versatile N-sulfonyliminium cation, possible. Full article
(This article belongs to the Special Issue Novel Studies of Organic Electrosynthesis)
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2223 KiB  
Proceeding Paper
In Silico Assessment of Enaminone–Sulfanilamides as Potential Carbonic Anhydrase II Inhibitors: Molecular Docking and ADMET Prediction
by Yousra Ouafa Bouone, Abdeslem Bouzina, Rachida Mansouri and Nour-Eddine Aouf
Chem. Proc. 2024, 16(1), 117; https://doi.org/10.3390/ecsoc-28-20211 - 14 Nov 2024
Viewed by 192
Abstract
Carbonic anhydrases (CAs) are a group of zinc-containing enzymes involved in many physiological processes through their role in the maintenance of the equilibrium between bicarbonate and CO2 levels. Human carbonic anhydrases (hCAs) are recognized as important drug targets due to their major [...] Read more.
Carbonic anhydrases (CAs) are a group of zinc-containing enzymes involved in many physiological processes through their role in the maintenance of the equilibrium between bicarbonate and CO2 levels. Human carbonic anhydrases (hCAs) are recognized as important drug targets due to their major implication in the development of diseases including cancer. Sulfanilamide derivatives have been widely studied and have shown remarkable efficiency in inhibiting carbonic anhydrases, with the presence of SO2NH2 in their structure. Therefore, the sulfonamide moiety is considered as the leading scaffold in the search for new hCA inhibitors. Moreover, the introduction of an enaminone to sulfonamide-based CA inhibitors showed an enhancement of inhibitory activity. In this context, we were interested in the in silico investigation of benzenesulfonamide derivatives containing β-enaminone that were synthesized from dicarbonyl compounds and sulfanilamide under microwave irradiation. The in silico assessment includes a molecular docking simulation against hCA II (PDB: 2AW1). The docked ligands showed good docking score values (−8.099 and −7.053 kcal.mol−1), which indicates a good stability of the studied compounds within the active site. Further, significant interactions with the residues of the active site were observed, including metal coordination with Zn 262, an H-bond with Thr 199, and pi–pi stacking with the side chain of His94, which are considered as the key interactions for CA inhibition. A complementary in silico study that involved ADMET prediction was performed to learn more about the pharmacokinetic properties and the toxicity of the products in order to comprehend their ability to become drug-candidates. Full article
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10 pages, 3112 KiB  
Article
Benchtop 19F Nuclear Magnetic Resonance (NMR) Spectroscopy-Optimized Knorr Pyrazole Synthesis of Celecoxib and Mavacoxib, 3-(Trifluoromethyl) Pyrazolyl Benzenesulfonamides, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
by Andrew Chyu, Selina Xi, Joshua Kim, Galen Liu, Indalina Chan, Seoyeon Hong, Allen Ke, Thomas Lavery, Anushree Marimuthu, Arjun Akula and Edward Njoo
Spectrosc. J. 2024, 2(4), 206-215; https://doi.org/10.3390/spectroscj2040014 - 11 Nov 2024
Viewed by 2999
Abstract
Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are [...] Read more.
Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are most commonly constructed through the cyclocondensation of a trifluorinated 1,3-dicarbonyl and an aryl hydrazine, are also found in numerous other drug candidates. Here, we interrogate the effects of solvents and the presence of Brønsted or Lewis acid catalysts on catalyzing this process. We highlight the utility of benchtop 19F NMR spectroscopy in enabling the real-time quantification of reaction progress and the identification of fluorinated species present in crude reaction mixtures without the need for cost-prohibitive deuterated solvents. Ultimately, we find that the reaction solvent has the greatest impact on the rate and product yield, and also found that the relationship between the keto-enol equilibrium of the dicarbonyl starting material pyrazole formation rate is highly solvent-dependent. More broadly, we describe the optimization of the yield and kinetics of trifluoromethylpyrazole formation in the synthesis of celecoxib and mavacoxib, which is made possible through high-throughput reaction screening on benchtop NMR. Full article
(This article belongs to the Special Issue Feature Papers in Spectroscopy Journal)
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17 pages, 6361 KiB  
Article
Supramolecular Structure of Sulfonamide-Substituted Silatranes: Quantum Chemical DFT Calculations
by Nina N. Chipanina, Sergey N. Adamovich, Arailym M. Nalibayeva, Yerlan N. Abdikalykov, Larisa P. Oznobikhina, Elizaveta N. Oborina and Igor B. Rozentsveig
Int. J. Mol. Sci. 2024, 25(22), 11920; https://doi.org/10.3390/ijms252211920 - 6 Nov 2024
Viewed by 1450
Abstract
The supramolecular structure of the crystal products–N-[2-chloro-2-(silatranyl)ethyl]-4-nitro-benzenesulfonamide 4d and N-chloro-N-[2-chloro-1-(silatran-1-yl-methyl)ethyl]benzene-sulfonamide 5a was established by X-ray diffraction analysis data, FTIR spectroscopy and DFT quantum chemical calculations. Their crystal lattice is formed by cyclic dimers with intermolecular hydrogen NH∙∙∙O-Si bonds [...] Read more.
The supramolecular structure of the crystal products–N-[2-chloro-2-(silatranyl)ethyl]-4-nitro-benzenesulfonamide 4d and N-chloro-N-[2-chloro-1-(silatran-1-yl-methyl)ethyl]benzene-sulfonamide 5a was established by X-ray diffraction analysis data, FTIR spectroscopy and DFT quantum chemical calculations. Their crystal lattice is formed by cyclic dimers with intermolecular hydrogen NH∙∙∙O-Si bonds and CH∙∙∙O=S short contacts. The distribution of electron density in the monomers was determined using quantum chemical calculations of their molecular electrostatic potential (MESP) in an isolated state (in gas) and in a polar medium. The transition from covalent N–Si bonds in crystal compounds and polar medium to non-covalent N∙∙∙Si bonds happened while performing the calculations on the monomer molecules and their dimers in gas. The effect of intermolecular interactions on the strength of the N–Si and N∙∙∙Si bonds in molecules was evaluated through calculations of their complexes with H2O and DMSO. Full article
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15 pages, 5035 KiB  
Article
Development and Optimization of a Redox Enzyme-Based Fluorescence Biosensor for the Identification of MsrB1 Inhibitors
by Hyun Bo Shim, Hyunjeong Lee, Hwa Yeon Cho, Young Ho Jo, Lionel Tarrago, Hyunggee Kim, Vadim N. Gladyshev and Byung Cheon Lee
Antioxidants 2024, 13(11), 1348; https://doi.org/10.3390/antiox13111348 - 2 Nov 2024
Viewed by 1508
Abstract
MsrB1 is a thiol-dependent enzyme that reduces protein methionine-R-sulfoxide and regulates inflammatory response in macrophages. Therefore, MsrB1 could be a promising therapeutic target for the control of inflammation. To identify MsrB1 inhibitors, we construct a redox protein-based fluorescence biosensor composed of [...] Read more.
MsrB1 is a thiol-dependent enzyme that reduces protein methionine-R-sulfoxide and regulates inflammatory response in macrophages. Therefore, MsrB1 could be a promising therapeutic target for the control of inflammation. To identify MsrB1 inhibitors, we construct a redox protein-based fluorescence biosensor composed of MsrB1, a circularly permutated fluorescent protein, and the thioredoxin1 in a single polypeptide chain. This protein-based biosensor, named RIYsense, efficiently measures protein methionine sulfoxide reduction by ratiometric fluorescence increase. We used it for high-throughput screening of potential MsrB1 inhibitors among 6868 compounds. A total of 192 compounds were selected based on their ability to reduce relative fluorescence intensity by more than 50% compared to the control. Then, we used molecular docking simulations of the compound on MsrB1, affinity assays, and MsrB1 activity measurement to identify compounds with reliable and strong inhibitory effects. Two compounds were selected as MsrB1 inhibitors: 4-[5-(4-ethylphenyl)-3-(4-hydroxyphenyl)-3,4-dihydropyrazol-2-yl]benzenesulfonamide and 6-chloro-10-(4-ethylphenyl)pyrimido[4,5-b]quinoline-2,4-dione. They are heterocyclic, polyaromatic compounds with a substituted phenyl moiety interacting with the MsrB1 active site, as revealed by docking simulation. These compounds were found to decrease the expression of anti-inflammatory cytokines such as IL-10 and IL-1rn, leading to auricular skin swelling and increased thickness in an ear edema model, effectively mimicking the effects observed in MsrB1 knockout mice. In summary, using a novel redox protein-based fluorescence biosensor, we identified potential MsrB1 inhibitors that can regulate the inflammatory response, particularly by influencing the expression of anti-inflammatory cytokines. These compounds are promising tools for understanding MsrB1’s role during inflammation and eventually controlling inflammation in therapeutic approaches. Full article
(This article belongs to the Special Issue Advances in Redox Biosensor)
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29 pages, 11564 KiB  
Article
Design, Synthesis, and Antimicrobial Evaluation of New Thiopyrimidine–Benzenesulfonamide Compounds
by Abdalrahman Khalifa, Manal M. Anwar, Walaa A. Alshareef, Eman A. El-Gebaly, Samia A. Elseginy and Sameh H. Abdelwahed
Molecules 2024, 29(19), 4778; https://doi.org/10.3390/molecules29194778 - 9 Oct 2024
Cited by 2 | Viewed by 2542
Abstract
Bacterial infection poses a serious threat to human life due to the rapidly growing resistance of bacteria to antibacterial drugs, which is a significant public health issue. This study was focused on the design and synthesis of a new series of 25 analogues [...] Read more.
Bacterial infection poses a serious threat to human life due to the rapidly growing resistance of bacteria to antibacterial drugs, which is a significant public health issue. This study was focused on the design and synthesis of a new series of 25 analogues bearing a 5-cyano-6-oxo-4-substituted phenyl-1,6-dihydropyrimidine scaffold hybridized with different substituted benzenesulfonamides through the thioacetamide linker M1–25. The antimicrobial activity of the new molecules was studied against various Gram-positive, Gram-negative, and fungal strains. All the tested compounds showed promising broad-spectrum antimicrobial efficacy, especially against K. pneumoniae and P. aeruginosa. Furthermore, the most promising compounds, 6M, 19M, 20M, and 25M, were subjected to minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. In addition, the antivirulence activity of the compounds was also examined using multiple biofilm assays. The new compounds promisingly revealed the suppression of microbial biofilm formation in the examined K. pneumoniae and P. aeruginosa microbial isolates. Additionally, in silico ADMET studies were conducted to determine their oral bioavailability, drug-likeness characteristics, and human toxicity risks. It is suggested that new pyrimidine–benzenesulfonamide derivatives may serve as model compounds for the further optimization and development of new antimicrobial and antisepsis candidates. Full article
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