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British Journal of Pharmacology Jun 2022RNA-binding motif protein 39 (RBM39) is an RNA-binding protein involved in transcriptional co-regulation and alternative RNA splicing. Recent studies have revealed that... (Review)
Review
RNA-binding motif protein 39 (RBM39) is an RNA-binding protein involved in transcriptional co-regulation and alternative RNA splicing. Recent studies have revealed that RBM39 is the unexpected target of aryl sulphonamides, which act as molecular glues between RBM39 and the DCAF15-associated E3 ubiquitin ligase complex leading to selective degradation of the target. Loss of RBM39 leads to aberrant splicing events and differential gene expression, thereby inhibiting cell cycle progression and causing tumour regression in a number of preclinical models. Many clinical studies have shown that aryl sulphonamides were well tolerated, but their clinical performance was limited due to an insufficient understanding of the target, RBM39 biology and a lack of predictive biomarkers. This review summarises the current knowledge of RBM39 function and discusses the therapeutic potential of this spliceosome target in cancer therapy. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc.
Topics: Alternative Splicing; Humans; Neoplasms; RNA-Binding Motifs; RNA-Binding Proteins; Sulfonamides
PubMed: 33238031
DOI: 10.1111/bph.15331 -
Bioorganic & Medicinal Chemistry Letters Mar 2022We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for...
We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC values <5 µM against ex vivo Schistosoma mansoni.
Topics: Animals; Carbolines; Dose-Response Relationship, Drug; Molecular Structure; Schistosoma mansoni; Structure-Activity Relationship; Sulfonamides
PubMed: 35031451
DOI: 10.1016/j.bmcl.2022.128546 -
Journal of Industrial Microbiology &... Jun 2021Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as... (Review)
Review
Sulfonamides and sulfamates are a group of organosulfur compounds that contain the signature sulfamoyl structural motif. These compounds were initially only known as synthetic antibacterial drugs but were later also discovered as natural products. Eight highly potent examples have been isolated from actinomycetes to date, illustrating the large biosynthetic repertoire of this bacterial genus. For the biosynthesis of these compounds, several distinct and unique biosynthetic machineries have been discovered, capable to generate the unique S-N bond. For the creation of novel, second generation natural products by biosynthetic engineering efforts, a detailed understanding of the underlying enzyme machinery toward potent structural motifs is crucial. In this review, we aim to summarize the current state of knowledge on sulfonamide and sulfamate biosynthesis. A detailed discussion for the secondary sulfamate ascamycin, the tertiary sulfonamide sulfadixiamycin A, and the secondary sulfonamide SB-203208 is provided and their bioactivities and mode of actions are discussed.
Topics: Actinobacteria; Anti-Bacterial Agents; Biological Products; Sulfonamides; Sulfonic Acids
PubMed: 33928358
DOI: 10.1093/jimb/kuab001 -
Future Medicinal Chemistry 2024Cancer as a devastating malignancy, seriously threatens human life and health, but most chemotherapeutics have long been criticized for unsatisfactory therapeutic... (Review)
Review
Cancer as a devastating malignancy, seriously threatens human life and health, but most chemotherapeutics have long been criticized for unsatisfactory therapeutic efficacy due to drug resistance and severe off-target toxicity. Pyrimidines, including fused pyrimidines, are privileged scaffolds for various biological cancer targets and are the most important class of metalloenzyme carbonic anhydrase inhibitors. Pyrimidine-sulfonamide hybrids can act on different targets in cancer cells simultaneously and possess potent activity against various cancers, revealing that hybridization of pyrimidine with sulfonamide is a promising approach to generate novel effective anticancer candidates. This review aims to summarize the recent progress of pyrimidine-sulfonamide hybrids with anticancer potential, covering papers published from 2020 to present, to facilitate further rational design of more effective candidates.
Topics: Humans; Sulfonamides; Pyrimidines; Antineoplastic Agents; Neoplasms; Carbonic Anhydrase Inhibitors; Molecular Structure; Animals
PubMed: 38624011
DOI: 10.4155/fmc-2024-0010 -
British Medical Journal Jun 1968
Topics: Agranulocytosis; Anemia, Aplastic; Anemia, Hemolytic; Crystallization; Drug Hypersensitivity; Drug Resistance, Microbial; Folic Acid Antagonists; Humans; Intestinal Absorption; Protein Binding; Stevens-Johnson Syndrome; Sulfadiazine; Sulfonamides; Urine
PubMed: 5658415
DOI: No ID Found -
Molecules (Basel, Switzerland) Jun 2024A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years....
A tumor-targeting fluorescent probe has attracted increasing interest in fluorescent imaging for the noninvasive detection of cancers in recent years. Sulfonamide-containing naphthalimide derivatives (SN-2NI, SD-NI) were synthesized by the incorporation of N-butyl-4-ethyldiamino-1,8-naphthalene imide (NI) into sulfonamide (SN) and sulfadiazine (SD) as the tumor-targeting groups, respectively. These derivatives were further characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (H NMR), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), and a fluorescence assay. In vitro properties, including cell cytotoxicity and the cell uptake of tumor cells, were also evaluated. Sulfonamide-containing naphthalimide derivatives possessed low cell cytotoxicity to B16F10 melanoma cells. Moreover, SN-2NI and SD-NI can be taken up highly by B16F10 cells and then achieve good green fluorescent images in B16F10 cells. Therefore, sulfonamide-containing naphthalimide derivatives can be considered to be the potential probes used to target fluorescent imaging in tumors.
Topics: Naphthalimides; Sulfonamides; Fluorescent Dyes; Animals; Mice; Cell Line, Tumor; Humans; Molecular Structure; Spectroscopy, Fourier Transform Infrared; Cell Survival
PubMed: 38930839
DOI: 10.3390/molecules29122774 -
Mini Reviews in Medicinal Chemistry 2018The serotonin system exerts its effects on the CNS and many peripheral systems. Of the 14 serotonin receptors, the 5-HT7 receptor is the most recently discovered. The... (Comparative Study)
Comparative Study Review
The serotonin system exerts its effects on the CNS and many peripheral systems. Of the 14 serotonin receptors, the 5-HT7 receptor is the most recently discovered. The 5-HT7 receptor has been shown to be involved in stress reduction, depression, and nociceptive control. Despite the 20 years since the discovery of 5-HT7R, there are still few truly selective ligands. Two of the common scaffolds for 5-HT7R ligands are long chain arylpiperazines (LCAPs) and sulfonamide containing compounds. This review focuses on recently developed (2014-2016) 5-HT7R ligands, their selectivity for the receptor, and suggests the possible new pharmacophore models for these ligands.
Topics: Drug Discovery; Humans; Ligands; Molecular Structure; Piperazine; Piperazines; Receptors, Serotonin; Structure-Activity Relationship; Sulfonamides
PubMed: 28901854
DOI: 10.2174/1389557517666170913111533 -
ChemistryOpen Mar 2025Molecular hybrids of diversely functionalized quinoline and sulfonamide have been designed. Multistep synthetic strategies have been used for the synthesis. The...
Molecular hybrids of diversely functionalized quinoline and sulfonamide have been designed. Multistep synthetic strategies have been used for the synthesis. The anti-cancer properties have been evaluated against various cancer cell lines including HCT116, A549, U2OS, CCRF-CEM, Jurkat, MOLT-4, RAMOS, and K562. Non-cancer cell lines MRC-5 and BJ were also included for comparison. When examining the effects on A549, HCT116, and U2OS cells, all tested compounds exhibited limited potency with IC values exceeding 50 μM, indicating weak activity against these cell lines. Against the ITK high cells Viz. are Jurkat, CCRF-CEM and MOLT-4, 9 e, 9 p and 9 j found to the maximum potent compounds with IC values of 7.43±7.40 μM, 13.19±1.25 μM and 5.57±7.56 μM respectively. Similarly, in the BTK high cells screenings, 9 n and 9 e molecules with an IC value of 2.76±0.79 μM and 5.47±1.71 μM against RAMOS and K562 respectively are highly potent. Interestingly, all the molecules have exhibited IC value >50 μM against the non-cancer cells (MRC-5 and BJ), which indicates the promising non-cytotoxic nature of the molecules.
Topics: Humans; Quinolines; Antineoplastic Agents; Sulfonamides; Drug Design; Drug Screening Assays, Antitumor; Cell Line, Tumor; Structure-Activity Relationship; Cell Proliferation
PubMed: 39600047
DOI: 10.1002/open.202400334 -
Scientific Reports Jun 2024In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives...
Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies.
In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, HNMR, CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D‑QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.
Topics: Quantitative Structure-Activity Relationship; Sulfonamides; Anti-Bacterial Agents; Benzopyrans; Apoptosis; Molecular Docking Simulation; Microbial Sensitivity Tests; Mice; Animals; Cell Line
PubMed: 38834651
DOI: 10.1038/s41598-024-63535-5 -
Molecules (Basel, Switzerland) Feb 2022Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique... (Review)
Review
Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.
Topics: Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Coumarins; Structure-Activity Relationship; Sulfonamides
PubMed: 35268704
DOI: 10.3390/molecules27051604