10269-25-7Relevant academic research and scientific papers
Abrogation of hyperosmotic impairment of insulin signaling by a novel class of 1,2-dithiole-3-thiones through the inhibition of S6K1 activation
Eun, Ju Bae,Yoon, Mee Yang,Sang, Geon Kim
, p. 1502 - 1512 (2008)
A previous study from this laboratory showed that oltipraz and synthetic dithiolethiones prevent tumor necrosis factor-α-induced hepatic insulin resistance via AMP-activated protein kinase-dependent p70S6 kinase (S6K) 1 inhibitory pathway. This study investigated whether oltipraz and a novel class of 1,2-dithiole-3-thiones were capable of preventing insulin resistance induced by hyperosmotic stress, thereby enhancing insulin-dependent signals, and, if so, whether the restoration of insulin signal was mediated with the inhibition of S6K1 activity stimulated by hyperosmotic stress. In HepG2 cells, oltipraz treatment inhibited insulin receptor substrate (IRS) 1 serine phosphorylation, a marker of insulin resistance, induced by sorbitol-, mannitol-, or sodium chloride-induced hyperosmotic stress. Consequently, this allowed cells to restore insulin signals, which was evidenced by decrease in the ratio of serine to tyrosine phosphorylations of IRS1 and increase in the phosphorylations of Akt and glycogen synthase kinase (GSK) 3β. Hyperosmotic stress markedly activated S6K1; S6K1 activation was completely abolished by oltipraz pretreatment. An experiment using dominant-negative S6K1 supports the essential role of S6K1 in the hyperosmolarity-stimulated phosphorylation of IRS1. Transfection of constitutive active mutant S6K1 eliminated the protective effect of oltipraz on GSK3β phosphorylation, indicating that oltipraz restores insulin signaling by inhibiting S6K1 activation. A variety of synthetic 1,2-dithiole-3-thione derivatives also inhibited S6K1 activity and insulin resistance induced by hyperosmotic stress in HepG2 cells. The results of this study demonstrate that a novel class of 1,2-dithiole-3-thiones improve insulin sensitivity under the condition of hyperosmotic stress, which results from the inhibition of S6K1 activation. Copyright
A New Synthesis of 3H-1,2-Dithiole-3-thiones
Curphey, Thomas J.,Joyner, H. Howard
, p. 3703 - 3706 (1993)
Exposure of 3-oxo dithioic acids to a solution of polysulfanes in liquid hydrogen sulfide gives 3H-1,2-dithiole-3-thiones in yields varying from poor to excellent.The method tolerates the presence of functional groups which are problematical for other met
Selective [3 + 2] Cycloaddition of Cyclopropenone Derivatives and Elemental Chalcogens
Wu, Jian,Gao, Wen-Xia,Huang, Xiao-Bo,Zhou, Yun-Bing,Liu, Miao-Chang,Wu, Hua-Yue
supporting information, p. 5555 - 5560 (2020/07/30)
A highly efficient method is disclosed for the synthesis of 1,2-dichalcogen heterocycles via [3 + 2] cycloaddition of cyclopropenone derivatives and elemental chalcogens. Different from other cyclopropenone derivatives, cyclopropenselenones undergo unprec
Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
, p. 2214 - 2231 (2020/03/06)
Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
Dianions of 3-oxodithioic acids: Preparation and conversion to 3H-1,2-dithiole-3-thiones
Curphey,Libby
, p. 6977 - 6980 (2007/10/03)
Reaction of ketones with CS2 and 2 equivalents of KH in THF-N,N'-dimethylpropyleneurea solution produces the dianions of 3-oxodithioic acids. These dianions are converted in good yield to 3H-1,2-dithiole-3-thiones by the sequential action of hexamethyldisilathiane and an oxidizing agent such as hexachloroethane. (C) 2000 Elsevier Science Ltd.
Synthesis of 3H-1,2-dithiole-3-thiones by a novel oxidative cyclization
Curphey, Thomas J.,Joyner, H. Howard
, p. 7231 - 7234 (2007/10/02)
Reaction of 3-oxo dithioic acids with a combination of hexamethyldisilathiane and N-chlorosuccinimide in the presence of a catalytic amount of imidazole brings about oxidative ring closure to 3H-1,2-dithiole-3-thiones. Yields vary from poor to good.
1,1',2,2'-Tetrathiafulvalenes, II. - Thienothiophenes from 1,2-Dithiole Compounds; 3H-1,2-Dithiol-3-ylidenes (1,2-Dithiole-3-carbenes) as Supposed Intermediates
Behringer, Hans,Meinetsberger, Eike
, p. 1729 - 1750 (2007/10/02)
3,3'-Bi(3H-1,2-dithiolylidenes) (1,1',2,2'-Tetrathiafulvalenes) 5 are not obtainable with the following reactions which, however, have proved to be a good approach to the corresponding 1,3-isomers 3: 1) Deprotonation of 1,2-dithiolylium cations 4, 2) pyrolysis of alkali derivatives from 1,2-dithiol-2-one tosylhydrazones 26 (Bamford-Stevens reaction), or 3) partial desulfuration of 1,2-dithiole-3-thiones 6 by means of trivalent phosphorus compounds.These reactions with the 1,2-isomers always yield thienothiophenes 8 accompanied by the related 1,2-dithiole-3-thiones 6 (1,2-trithiones) and in the case of 26 also by azines 27.Partial desulfuration of 1,2-trithiones 6 by copper bronze again yields the corresponding thienothiophenes 8 instead of 5.Thermal decomposition of the 1,2-dithiolylium iodide 34 or 34' yields the thienothiophene 8a together with the 1,2-trithione 6a.Surprisingly, the P4S10-sulfuration of "desaurines" 37 gives thienothiophenes again and also 1,2-dithiole-3-thiones 6. - 1-Morpholinocyclohexene (18) reacts with the 1,2-dithiolylium cation 4a (X = ClO4) to give a formal 1:1 adduct from the carbene 9a and the enamine for which the structure 19 is proposed.
1,1'2,2'-Tetrathiafulvalenes, III. - Syhthesis, Properties, and Reactions of 3,3'-Bi(3H-1,2-dithiolylidenes)(1,1',2,2'-Tetrathiafulvalenes)
Behringer, Hans,Meinetsberger, Eike
, p. 1928 - 1959 (2007/10/02)
1,1',2,2'-tetrathiafulvalenes 1 can be prepared by different methods from the cations of 1,2-dithiolylium salts 4 which are either unsubstituted or appropriate substituted in 3-position (instead of 3-Cl also H or SCH3).The structure of 1 is substantiated by chemical arguments.IR and 13C-NMR spectra support the absence of thioxo groups. - Like the 1,1',3,3'-isomers 2 the 1,1',2,2'-tetrathiafulvalenes are disposed to stepwise donation of electrons with formation of the radical cation and dication salts 25 or 11, respectively, as well as to the formation of charge transfer complexes with tetracyanoethylene, tetracyanoquinodimethane, and 2,3-dichloro-5,6-dicyanobenzoquinone.Tris(triphenylphosphine)rhodium(I) chloride and tetrakis(triphenylphosphine)platinum(O) yield complexes with 1a. - Thermolysis of 1 produces thienothiophenes 6.Partial desulfuration of 1a, for example, is also feasible with oxidizing agents like lead(IV) acetate.Selenium dioxide, however, gives the corresponding thienofuran 41.The reaction with trialkyl phosphites yields a disulfide - probably the 2,2'-bi(2H-thietylidene) 38 - the thermolysis of which gives the thienothiophene 6a. - Compounds 1a and 1c do not react with dimethyl acetylenedicarboxylate, isothiocyanate, several 1,3-dipoles (azides), and also not with elementary sulfur, however, 1e forms with sulfur the 3H-1,2-dithiol-3-thione 5e (X = S).
MECHANISM OF THE REACTION OF 4- AND 5-ARYLTRITHIONES WITH 4-PHENYL-1,2,4-TRIAZOLINE-3,5-DIONE
Drozd, V. N.,Fedoseev, V. V.,Bogomolova, G. S.,Sergeichuk, V. V.,Semenenko, N. M.,Mandrugin, A. A.
, p. 188 - 191 (2007/10/02)
The reaction of 4- and 5-aryl-1,2-dithiolene-3-thiones (trithiones) with 4-phenyl-1,2,4-triazoline-3,5-dione occurs with the ejection of the exocyclic sulfur atom and the formation of 4-phenyl-1-urazolides.
