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European Journal of Medicinal Chemistry Feb 2019Tamiflu readily undergoes endogenous hydrolysis to give oseltamivir carboxylic acid (OC) as the active anti-influenza agent to inhibit the viral neuraminidase (NA). GOC...
Tamiflu readily undergoes endogenous hydrolysis to give oseltamivir carboxylic acid (OC) as the active anti-influenza agent to inhibit the viral neuraminidase (NA). GOC is derived from OC by replacing the 5-amino group with a guanidino group. In this study, OC and GOC congeners with the carboxylic acid bioisosteres of boronic acid, trifluoroborate, sulfone, sulfinic acid, sulfonic acid and sulfonate ester were first synthesized, starting with conversion of OC to a Barton ester, followed by halodecarboxylation to give the iodocyclohexene, which served as a pivotal intermediate for palladium-catalyzed coupling reactions with appropriate diboron and thiol reagents. The enzymatic and cell-based assays indicated that the GOC congeners consistently displayed better NA inhibition and anti-influenza activity than the corresponding OC congeners. The GOC sulfonic acid congener (7a) was the most potent anti-influenza agent, showing EC = 2.2 nM against the wild-type H1N1 virus, presumably because the sulfonic acid 7a was more lipophilic than GOC and exerted stronger interactions on the three arginine residues (R118, R292 and R371) in the NA active site. Although the trifluoroborates, sulfones and sulfonate esters did not have acidic proton, they still exhibited appreciable NA inhibitory activity, indicating that the polarized B-F and S→O bonds still made sufficient interactions with the tri-arginine motif.
Topics: Antiviral Agents; Boronic Acids; Carboxylic Acids; Enzyme Inhibitors; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Neuraminidase; Oseltamivir; Structure-Activity Relationship; Sulfones; Sulfonic Acids; Sulfur Compounds
PubMed: 30576902
DOI: 10.1016/j.ejmech.2018.12.027 -
FEMS Microbiology Reviews Dec 1998Organosulfonates are widespread compounds, be they natural products of low or high molecular weight, or xenobiotics. Many commonly found compounds are subject to... (Review)
Review
Organosulfonates are widespread compounds, be they natural products of low or high molecular weight, or xenobiotics. Many commonly found compounds are subject to desulfonation, even if it is not certain whether all the corresponding enzymes are widely expressed in nature. Sulfonates require transport systems to cross the cell membrane, but few physiological data and no biochemical data on this topic are available, though the sequences of some of the appropriate genes are known. Desulfonative enzymes in aerobic bacteria are generally regulated by induction, if the sulfonate is serving as a carbon and energy source, or by a global network for sulfur scavenging (sulfate-starvation-induced (SSI) stimulon) if the sulfonate is serving as a source of sulfur. It is unclear whether an SSI regulation is found in anaerobes. The anaerobic bacteria examined can express the degradative enzymes constitutively, if the sulfonate is being utilized as a carbon source, but enzyme induction has also been observed. At least three general mechanisms of desulfonation are recognisable or postulated in the aerobic catabolism of sulfonates: (1) activate the carbon neighboring the C-SO3- bond and release of sulfite assisted by a thiamine pyrophosphate cofactor; (2) destabilize the C-SO3- bond by addition of an oxygen atom to the same carbon, usually directly by oxygenation, and loss of the good leaving group, sulfite; (3) an unidentified, formally reductive reaction. Under SSIS control, different variants of mechanism (2) can be seen. Catabolism of sulfonates by anaerobes was discovered recently, and the degradation of taurine involves mechanism (1). When anaerobes assimilate sulfonate sulfur, there is one common, unknown mechanism to desulfonate the inert aromatic compounds and another to desulfonate inert aliphatic compounds; taurine seems to be desulfonated by mechanism (1).
Topics: Alkanesulfonates; Bacteria, Anaerobic; Biodegradation, Environmental; Fermentation; Oxidation-Reduction
PubMed: 9990724
DOI: 10.1111/j.1574-6976.1998.tb00378.x -
Environmental Health Perspectives Nov 2022
Topics: Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates
PubMed: 36331817
DOI: 10.1289/EHP12012 -
Bioorganic & Medicinal Chemistry Letters Jun 2011Structure stability/activity relationships (SXR) of a new class of N,N-dichloroamine compounds were explored to improve antimicrobial activity against Escherichia coli,...
Structure stability/activity relationships (SXR) of a new class of N,N-dichloroamine compounds were explored to improve antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans while maintaining aqueous solution stability. This study identified a new class of solution-stable and topical antimicrobial agents. These agents are sulfone-stabilized and possess either a quaternary ammonium or sulfonate appendages as a water solubilizing group. Several unique challenges were confronted in the synthesis of these novel compounds which are highlighted in the discussion.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Chloramines; Drug Stability; Escherichia coli; Molecular Structure; Staphylococcus aureus; Structure-Activity Relationship; Sulfones; Water
PubMed: 21570284
DOI: 10.1016/j.bmcl.2011.04.084 -
Annual Review of Biochemistry Jun 2021Sulfonates include diverse natural products and anthropogenic chemicals and are widespread in the environment. Many bacteria can degrade sulfonates and obtain sulfur,... (Review)
Review
Sulfonates include diverse natural products and anthropogenic chemicals and are widespread in the environment. Many bacteria can degrade sulfonates and obtain sulfur, carbon, and energy for growth, playing important roles in the biogeochemical sulfur cycle. Cleavage of the inert sulfonate C-S bond involves a variety of enzymes, cofactors, and oxygen-dependent and oxygen-independent catalytic mechanisms. Sulfonate degradation by strictly anaerobic bacteria was recently found to involve C-S bond cleavage through O-sensitive free radical chemistry, catalyzed by glycyl radical enzymes (GREs). The associated discoveries of new enzymes and metabolic pathways for sulfonate metabolism in diverse anaerobic bacteria have enriched our understanding of sulfonate chemistry in the anaerobic biosphere. An anaerobic environment of particular interest is the human gut microbiome, where sulfonate degradation by sulfate- and sulfite-reducing bacteria (SSRB) produces HS, a process linked to certain chronic diseases and conditions.
Topics: Acetyltransferases; Alkanesulfonates; Anaerobiosis; Bacteria; Carbon-Carbon Lyases; Gastrointestinal Microbiome; Glycine; Humans; Hydrogen Sulfide; Isethionic Acid; Microbiota; Sulfonic Acids; Taurine
PubMed: 33823652
DOI: 10.1146/annurev-biochem-080120-024103 -
International Journal of Biological... Dec 2023Polysaccharides, as biological macromolecules, are widely found in plants, animals, fungi, and bacteria and exhibit various biological activities. However, many natural... (Review)
Review
Polysaccharides, as biological macromolecules, are widely found in plants, animals, fungi, and bacteria and exhibit various biological activities. However, many natural polysaccharides exhibit low or non-existent biological activities because of their high molecular weights and poor water solubility, limiting their application in many fields. Sulfonation is one of the most effective chemical modification methods to improve physicochemical properties and biological activities of natural polysaccharides or even impart natural polysaccharides with new biological activities. Therefore, sulfonated polysaccharides have attracted increasing attention because of their antioxidant, anticoagulant, antiviral, and immunomodulatory properties. This paper reviews the recent advances in the sulfonation of polysaccharides, including preparation, characterization, and biological activities of sulfonated polysaccharides, and provides a theoretical basis for wide applications of sulfonated polysaccharides.
Topics: Animals; Plants; Bacteria; Alkanesulfonates; Chemical Phenomena; Polysaccharides
PubMed: 37611689
DOI: 10.1016/j.ijbiomac.2023.126400 -
Current Organic Synthesis 2020The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on... (Review)
Review
BACKGROUND
The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on developing efficient procedures for preparation of organic sulfones.
MATERIALS AND METHODS
Water, a proton source, is considered one of the most ideal and promising solvents in organic synthesis for its easy availability, low cost, nontoxic and nonflammable characteristics. From the green and sustainable point of view, more and more reactions are designed proceeding in water.
OBJECTIVE
The review focuses on recent advances of sulfonylation reactions proceeding in water. Sulfonylation reactions using sodium sulfinates, sulfonyl hydrazides, sulfinic acids, and sulfonyl chlorides as sulfonating agents were introduced in detail.
RESULTS AND DISCUSSION
In this review, sulfonylation reactions proceeding in water developed in recent four yields were presented. Sulfonylation reactions using water as solvent have attracted more and more attention because water is one of the most ideal and promising solvents in organic synthesis for its facile availability, low cost, nontoxic and nonflammable properties.
CONCLUSION
Numerous sulfonating agents such as sodium sulfinates, sulfonyl hydrazides, sulfinic acid, sulfonyl chlorides and disulfides are efficient for sulfonylation reactions which proceed in water.
Topics: Green Chemistry Technology; Sulfones; Water
PubMed: 32178616
DOI: 10.2174/1570179417666200316124107 -
International Journal of Biological... Mar 2024Membrane-based polyether sulfone (PES) is a potential candidate for hemodialysis because of its properties such as high mechanical strength, thermal stability, and...
Membrane-based polyether sulfone (PES) is a potential candidate for hemodialysis because of its properties such as high mechanical strength, thermal stability, and chemical resistance. However, the nature of the hydrophobicity in the PES membrane inhibits their performance in transporting creatinine. In this study, polyethersulfone (PES) membranes were modified using a sulfonation process and the addition of chitosan (CS) and lithium chloride (LiCl) to improve its performance in transporting creatinine. The FTIR spectrum of the modified membrane shows peaks of the sulfonate (-SO), amine (NH), and hydroxyl (-OH) groups in absorption areas of 1065 cm, 1650 cm, and 3384 cm, respectively, indicating that the membrane SPES/CS-LiCl has been successfully prepared. The modified PES membranes shows a higher porosity, swelling, water absorption, and hydrophilicity than pure PES membrane. The modification of the PES membrane in this study also enhances the ability of the membrane to transport creatinine. In the pure PES membrane, the creatinine clearance is 0.30 mg/dL, while in the SPES/CS-LiCl (5:2) membrane the creatinine clearance is 0.42 mg/dL.
Topics: Chitosan; Creatinine; Lithium Chloride; Polymers; Sulfones
PubMed: 38296137
DOI: 10.1016/j.ijbiomac.2024.129784 -
Archives of Microbiology Dec 2002Organosulfonates are widespread in the environment, both as natural products and as xenobiotics; and they generally share the property of chemical stability. A wide... (Review)
Review
Organosulfonates are widespread in the environment, both as natural products and as xenobiotics; and they generally share the property of chemical stability. A wide range of phenomena has evolved in microorganisms able to utilize the sulfur or the carbon moiety of these compounds; and recent work has centered on bacteria. This Mini-Review centers on bacterial catabolism of the carbon moiety in the C2-sulfonates and the fate of the sulfonate group. Five of the six compounds examined are subject to catabolism, but information on the molecular nature of transport and regulation is based solely on sequencing data. Two mechanisms of desulfonation have been established. First, there is the specific monooxygenation of ethanesulfonate or ethane-1,2-disulfonate. Second, the oxidative, reductive and fermentative modes of catabolism tend to yield the intermediate sulfoacetaldehyde, which is now known to be desulfonated to acetyl phosphate by a thiamin-diphosphate-dependent acetyltransferase. This enzyme is widespread and at least three subgroups can be recognized, some of them in genomic sequencing projects. These data emphasize the importance of acetyl phosphate in bacterial metabolism. A third mechanism of desulfonation is suggested: the hydrolysis of sulfoacetate.
Topics: Acetaldehyde; Alkanesulfonates; Bacteria; Bacteria, Aerobic; Biodegradation, Environmental; Molecular Structure; Sulfites; Sulfonic Acids
PubMed: 12471498
DOI: 10.1007/s00203-002-0497-0 -
Carbohydrate Polymers Apr 2016To balance the relationship among proton conductivity and mechanic strength of sulfonated poly(ether sulfone) (SPES) membrane, chitin nanowhisker-supported nanocomposite...
To balance the relationship among proton conductivity and mechanic strength of sulfonated poly(ether sulfone) (SPES) membrane, chitin nanowhisker-supported nanocomposite membranes were prepared by incorporating whiskers into SPES. The as-prepared chitin whiskers were prepared by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) mediated oxidation of α-chitin from crab shells. The structure and properties of the composite membranes were examined as proton exchange membrane (PEM). Results showed that chitin nanowhiskers were dispersed incompactly in the SPES matrix. Thermal stability, mechanical properties, water uptake and proton conductivity of the nanocomposite films were improved from those of the pure SPES film with increasing whisker content, which ascribed to strong interactions between whiskers and between SPES molecules and chitin whiskers via hydrogen bonding. These indicated that composition of filler and matrix got good properties and whisker-supported membranes are promising materials for PEM.
Topics: Chitin; Cyclic N-Oxides; Electric Power Supplies; Mechanical Phenomena; Membranes, Artificial; Nanostructures; Oxidation-Reduction; Polymers; Protons; Sulfones; Sulfonic Acids; Temperature; Water
PubMed: 26876844
DOI: 10.1016/j.carbpol.2015.12.029