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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 -
Chemical & Pharmaceutical Bulletin 2021Natural products are an important source of medicinal seeds. The discovery of novel biosynthetic enzymes from nature is important for their use as biocatalysts for the... (Review)
Review
Natural products are an important source of medicinal seeds. The discovery of novel biosynthetic enzymes from nature is important for their use as biocatalysts for the enzymatic synthesis of useful natural products. In addition, genetics and structural biology developments have enabled the engineering of enzymes for the production of unnatural analogs of bioactive natural products. In this review, I describe the recent research on these two topics, the exploitation of a novel secondary metabolite enzyme involved in the biosynthesis of the sulfonamide natural product antibiotic SB-203208, and the production of unnatural bioactive depsipeptides by reconstruction of the modular enzyme assembly lines in the microbial host.
Topics: Anti-Bacterial Agents; Biological Products; Depsipeptides; Indenes; Molecular Conformation; Sulfonamides
PubMed: 33952851
DOI: 10.1248/cpb.c21-00032 -
Molecules (Basel, Switzerland) Dec 2022Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis... (Review)
Review
Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis has received a "second wind", due to the increase in the synthetic capabilities of organic chemistry and the study of their medical and biological properties of a wide spectrum of biological activity. New reagents and new reactions make it possible to significantly increase the number of compounds with a sulfonamide fragment in combination with other important pharmacophore groups, such as, for example, a wide class of -containing heterocycles. The result of these synthetic possibilities is the extension of the activity spectrum-along with antibacterial activity, many of them exhibit other types of biological activity. Antiviral activity is also observed in a wide range of sulfonamide derivatives. This review provides examples of the synthesis of sulfonamide compounds with antiviral properties that can be used to develop drugs against coxsackievirus B, enteroviruses, encephalomyocarditis viruses, adenoviruses, human parainfluenza viruses, Ebola virus, Marburg virus, SARS-CoV-2, HIV and others. Since over the past three years, viral infections have become a special problem for public health throughout the world, the development of new broad-spectrum antiviral drugs is an extremely important task for synthetic organic and medicinal chemistry. Sulfonamides can be both sources of nitrogen for building a nitrogen-containing heterocyclic core and the side chain substituents of a biologically active substance. The formation of the sulfonamide group is often achieved by the reaction of the -nucleophilic center in the substrate molecule with the corresponding sulfonylchloride. Another approach involves the use of sulfonamides as the reagents for building a nitrogen-containing framework.
Topics: Humans; Antiviral Agents; Sulfonamides; COVID-19; SARS-CoV-2; Sulfanilamide; Anti-Bacterial Agents; Indicators and Reagents; Nitrogen
PubMed: 36615245
DOI: 10.3390/molecules28010051 -
Journal of Enzyme Inhibition and... Dec 2022The mitochondrial isoforms VA/VB of metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) are involved in metabolic processes, such as lipogenesis and fatty acid... (Review)
Review
The mitochondrial isoforms VA/VB of metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) are involved in metabolic processes, such as lipogenesis and fatty acid biosynthesis. We review the drug design landscape for obtaining CA VA/VB-selective/effective inhibitors, starting from the clinical observations that CA inhibitory drugs, such as the antiepileptics topiramate and zonisamide, or the diuretic acetazolamide induce a significant weight loss. The main approaches for designing such compounds consisted in drug repurposing of already known CA inhibitors (CAIs); screening of synthetic/natural products libraries both in the classical and virtual modes, and drug design using the tail approach. A number of such studies allowed the identification of lead compounds diverse from sulphonamides, such as tropolones, phenols, polyphenols, flavones, glycosides, fludarabine, lenvatinib, rufinamide, etc., for which the binding mode to the enzyme is not always well understood. Classical drug design studies of sulphonamides, sulfamates and sulfamides afforded low nanomolar mitochondrial CA-selective inhibitors, but detailed antiobesity studies were poorly performed with most of them. A breakthrough in the field may be constituted by the design of hybrids incorporating CAIs and other antiobesity chemotypes.
Topics: Anti-Obesity Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Humans; Obesity; Sulfonamides
PubMed: 36073149
DOI: 10.1080/14756366.2022.2121393 -
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 -
Molecules (Basel, Switzerland) Jun 2022Sulfonamides are a classic group of chemotherapeutic drugs with a broad spectrum of pharmacological action, including anticancer activity. In this work, reversed-phase...
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 log, employing various computational approaches. Similarities and dissimilarities between experimental and computational log 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.
Topics: Chemometrics; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Cluster Analysis; Humans; Principal Component Analysis; Quantitative Structure-Activity Relationship; Sulfonamides
PubMed: 35807212
DOI: 10.3390/molecules27133965 -
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 -
Molecules (Basel, Switzerland) Apr 2023The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In... (Review)
Review
The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In particular, five-membered heterocyclic sulfonamides have been generally shown to be more effective inhibitors compared to six-membered rings ones. Despite the importance of oxygen and nitrogen five-membered heterocyclic aromatic rings in medicinal chemistry, the installation of sulfonamide moiety on such heterocycles has not received much attention. On the other hand, 1,3,4-thiadiazole/thiadiazoline ring-bearing sulfonamides are the scaffolds which have been widely used in a variety of pharmaceutically important CAIs such as acetazolamide, metazolamide and their many derivatives obtained by using the tail approach. Here, we reviewed the field focusing on the diverse biological activities of these CAIs, such as antiglaucoma, antiepileptic, antitumor and antiinfective properties. This review highlights developments involving five-membered heterocyclic sulfonamides over the last years, with a focus on their pharmacological/clinical applications.
Topics: Carbonic Anhydrase Inhibitors; Sulfonamides; Structure-Activity Relationship; Acetazolamide; Anticonvulsants; Sulfanilamide; Dermatologic Agents
PubMed: 37049983
DOI: 10.3390/molecules28073220