The use of Spheroids in the Study of Invasion
Rolf Bjerkvig in Spheroid Culture in Cancer Research, 2017
Poor solubility in water makes direct addition of a powdery drug to the culture medium impractical for testing its effect on invasion in vitro. In these cases organic solvents are used to prepare intermediate stock solutions of the drug. Dimethyl sulfoxide (DMSO) is often used, since it has two advantages. DMSO is an excellent solvent for most drugs, and the stock solution obtained is sterile. However, DMSO has been reported to be a differentiating agent, and its possible effects on invasion should be tested separately whenever it is used as a drug solvent in confronting cultures. In our hands no effect on invasion was detected for DMSO concentrations up to 1% in culture medium (v/v). Other drug solvents, such as ethanol or sodium hydroxyde solutions, are used in selected cases only.
Sutezolid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Sutezolid is rapidly oxidized to an active sulfoxide metabolite (PNU-101603). The sulfoxide metabolite contributes to its antimycobacterial activity (Barbachyn et al., 1996; Wallis et al., 2010), but does not alone account for its reported superiority over linezolid in both murine (Williams et al., 2009b) and ex vivo whole blood culture (Wallis et al., 2011) models. Pharmacokinetic-pharmacodynamic modeling studies suggest sutezolid’s superior efficacy is due to the potency of the parent molecule against intracellular M. tuberculosis, despite the significantly higher concentrations of the sulfoxide metabolite that likely contributes more to bactericidal activity against extracellular bacteria (Zhu et al., 2014).
Chemistries of Chemical Warfare Agents
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
Sulfides, including sulfur mustard, undergo oxidation at their sulfur atom position. Initial oxidation produces a sulfoxide, whereas further oxidation produces a sulfone as shown in the following reaction. Oxidants that can participate in such reactions include hydrogen peroxide, peroxyacids, nitric acid, permanganate ions, ozone, dinitrogen tetroxide, and dichromate ions. Oxides of sulfur mustard are not as volatile as mustard, which might possibly explain why the surfaces of British air raid shelters were sometimes coated with the oxidant calcium hypochlorite, Ca(OCl)2. Episulfonium ion formation is less likely in the sulfoxide of sulfur mustard than in sulfur mustard itself.
How do we address neglected sulfur pharmacophores in drug discovery?
Published in Expert Opinion on Drug Discovery, 2021
Michael J. Tilby, Michael C. Willis
A significant limitation in the development of sulfoximine-containing drugs has been the lack of synthetic routes to access this functional group. Traditional syntheses of these molecules involve the imination of sulfoxides (C). However, this approach is limited by the formation of N-substituted sulfoximines, which require further deprotection and functionalisation. In addition, toxic and explosive reagents are required [9]. In recent years, several breakthroughs have been achieved that allow rapid access to free (N-H) sulfoximines, under milder conditions, including the direct oxidation from thioethers (B) [10,11]. Furthermore, a recent alternative synthesis paired simple organometallic reagents with a high oxidation state sulfur linchpin reagent, ‘BiPhONSO’ [12]. Strategies based on sulfonamidate [13] and sulfinamide [14] intermediates have also enjoyed recent success.
Sterigmatocystin-induced DNA damage triggers cell-cycle arrest via MAPK in human neuroblastoma cells
Published in Toxicology Mechanisms and Methods, 2021
Veronica Zingales, Mónica Fernández-Franzón, Maria-José Ruiz
The reagent grade chemicals and cell culture compounds used, namely culture medium DMEM Ham’s-F12, penicillin, streptomycin, trypsin/EDTA solutions, phosphate buffer saline (PBS), fetal bovin serum (FBS), trizma base (Tris), propidium iodide (PI), Ribonuclease A (RNase), t-octylphenoxypolyethoxyethanol (Triton-X 100), 4′,6-diamidine-2′-phenylindole dihydrochloride (DAPI), SB203580 (p38 inhibitor), PD98059 (ERK inhibitor), SP600125 (JNK inhibitor), PFT (p53 inhibitor), agarose, low gelling temperature agarose (LMA), disodium ethylenediaminetetraacetate dihydrate (Na2-EDTA), sodium dihydrogen phosphate (NaH2PO4), disodium hydrogen phosphate (Na2HPO4) and paraformaldehyde were from Sigma Chemical Co (St. Louis, MO). Ethanol (EtOH) and sodium hydroxide (NaOH) were from Merck KGaA (Gernsheim, Germany). Dimethyl sulfoxide (DMSO) was obtained from Fisher Scientific (Geel, Belgium). Methanol (MeOH), sodium chloride (NaCl) and hydrochloric acid (HCl) were from VWR International (LLC, Monroeville, PA). The Litron In Vitro Microflow Kit for the micronucleus assay by flow cytometry was purchased from the Litron Laboratories (Litron Laboratories, Rochester, NY). The primary monoclonal antibody rabbit anti-human phospho-histone H2AX (Ser-139) was purchased from Cell Signaling Technology (Beverly, MA). Standard of the selected mycotoxin STE (MW: 324.28 g/mol) was purchased from Sigma-Aldrich (St. Louis, MO). Stock solutions of the mycotoxin were prepared in methanol and maintained at −20 °C.
Phenylalanine 4-monooxygenase: the “sulfoxidation polymorphism”
Published in Xenobiotica, 2020
Stephen C. Mitchell, Glyn B. Steventon
Methylene blue was the first xenobiotic cited in the literature as undergoing oxygenation at the sulfur moiety (Underhill & Closson, 1905). The metabolite referred to as methylene azure was presumed to be the sulfone derivative (Williams, 1959), but now the several methylene azures (and thionine) are recognised as a series of sequential N-demethylated products (Disanto & Wagner, 1972). Likewise, the sulfone of mustard gas, presumably formed via the sulfoxide, was postulated in a 1921 publication but was not experimentally confirmed at that time (Flury & Wieland, 1921). However, later work has shown the existence of both these sulfoxide and sulfone metabolites (Davison et al., 1961; Somani & Babu, 1989). The first demonstration of the in vivo formation of a xenobiotic sulfoxide metabolite was that of the anthelmintic, phenothiazine, reported in 1947 (Clare, 1947). This compound itself enjoyed a period of widespread fame as an effective vermifuge but is now known mainly as the parent molecule of a host of clinically useful phenothiazine drugs.
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