113239-57-9Relevant academic research and scientific papers
Overcoming resistance to cisplatin by inhibition of glutathione S-transferases (GSTs) with ethacraplatin micelles in?vitro and in?vivo
Li, Shuyi,Li, Chan,Jin, Shubin,Liu, Juan,Xue, Xiangdong,Eltahan, Ahmed Shaker,Sun, Jiadong,Tan, Jingjie,Dong, Jinchen,Liang, Xing-Jie
, p. 119 - 129 (2017)
Platinum-based DNA-adducting agents are used extensively in the clinic for cancer chemotherapy. However, the anti-tumor efficacy of these drugs is severely limited by cisplatin resistance, and this can lead to the failure of chemotherapy. One of cisplatin
Rational design of platinum(IV) compounds to overcome glutathione-S- transferase mediated drug resistance
Wee, Han Ang,Khalaila, Isam,Allardyce, Claire S.,Juillerat-Jeanneret, Lucienne,Dyson, Paul J.
, p. 1382 - 1383 (2005)
A rationally designed Pt(IV) anticancer compound is described, employing the novel concept of tethering an inhibitor of glutathione-S-transferase, an enzyme associated with Pt-based drug-resistance, to cisplatin. Its enzyme inhibition activity, investigat
Novel antiglaucoma prodrugs and codrugs of ethacrynic acid
Cynkowska, Grazyna,Cynkowski, Tadeusz,Al-Ghananeem, Abeer A.,Guo, Hong,Ashton, Paul,Crooks, Peter A.
, p. 3524 - 3527 (2005)
The purpose of this study was to synthesize a novel prodrug of ethacrynic acid (ECA) with short chain polyethylene glycols (PEGs) and codrugs of ECA with the β-adrenergic blocking agent atenolol (ATL) or timolol (TML) to overcome the adverse effects of EC
A general strategy to add diversity to ruthenium arene complexes with bioactive organic compounds: Via a coordinated (4-hydroxyphenyl)diphenylphosphine ligand
Biancalana, Lorenzo,Batchelor, Lucinda K.,De Palo, Alice,Zacchini, Stefano,Pampaloni, Guido,Dyson, Paul J.,Marchetti, Fabio
, p. 12001 - 12004 (2017)
Esterification of (4-hydroxyphenyl)diphenylphosphine, coordinated to the [Ru(η6-p-cymene)Cl2] fragment, allows a series of bioactive carboxylic acids to be introduced directly into the organometallic molecule. Evaluation of the compounds on human ovarian cancer cells reveals synergistic enhancements in their antiproliferative activity relative to their bioactive organic and organometallic precursors.
Development of an Efficient Dual-Action GST-Inhibiting Anticancer Platinum(IV) Prodrug
Lee, Keefe Guang Zhi,Babak, Maria V.,Weiss, Andrea,Dyson, Paul J.,Nowak-Sliwinska, Patrycja,Montagner, Diego,Ang, Wee Han
, p. 1210 - 1217 (2018/06/04)
The cytotoxicity of cisplatin (cDDP) is enhanced when co-administered with ethacrynic acid (EA), a glutathione S-transferase (GST) inhibitor. A PtIV–EA conjugate containing a cDDP core and two axial ethacrynate ligands (compound 1) was shown to be an excellent inhibitor of GST, but did not readily release a PtII species to exert a synergistic cytotoxic effect. In this study, a redesigned PtIV construct composed of a cDDP core with one axial ethacrynate ligand and one axial hydroxido ligand (compound 2) was prepared and shown to overcome the limitations of compound 1. The EA ligand in 2 is readily released in vitro together with a cytotoxic PtII species derived from cisplatin, working together to inhibit cell proliferation in cDDP-resistant human ovarian cancer cells. The in vitro activity translates well in vivo with 2, showing effective (～80 %) inhibition of tumor growth in a human ovarian carcinoma A2780 tumor model, while showing considerably lower toxicity than cisplatin, thus validating the new design strategy.
Environmental-protection preparation method for high yielding of 1,2,4-oxadiazole compounds containing alpha,beta-unsaturated ketones
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Paragraph 0084; 0085; 0089; 0093, (2017/08/30)
The invention provides an environmental-protection preparation method for high yielding of 1,2,4-oxadiazole compounds containing alpha,beta-unsaturated ketones; with 2,3-dichlorophenol as a raw material, an intermediate 5 is obtained through methylation and protection of phenolic hydroxyl groups, Friedel-Crafts acylation, methyl protecting group removal, nucleophilic substitution, ester hydrolysis, aldol condensation and dehydration reaction and then undergoes cyclization reaction with substituted amine oxime to obtain the target products 6r, 6s and 6u. The method has the advantages of mild reaction conditions, has no use of first-class reagents and other reagents harmful on the environment and operating personnel, fewer by-products, stable and controllable reactions, simple postprocessing, high yield and purity, and easy industrialized production.
Novel oxadiazole analogues derived from ethacrynic acid: Design, synthesis, and structure - Activity relationships in inhibiting the activity of glutathione S-transferase P1-1 and cancer cell proliferation
Yang, Xinmei,Liu, Guyue,Li, Hongcai,Zhang, Yun,Song, Dandan,Li, Chunmin,Wang, Rui,Liu, Bo,Liang, Wen,Jing, Yongkui,Zhao, Guisen
experimental part, p. 1015 - 1022 (2010/08/06)
Ethacrynic acid (EA) is a glutathione S-transferase P1-1 (GST P1-1) inhibitor with weak antiproliferative ability in tumor cells. By use of the principle of bioisosterism, a series of novel EA oxadiazole analogues were designed and synthesized. The struct
Drug delivery of lipophilic pyrenyl derivatives by encapsulation in a water soluble metalla-cage
Mattsson, Johan,Zava, Olivier,Renfrew, Anna K.,Sei, Yoshihisa,Yamaguchi, Kentaro,Dyson, Paul J.,Therrien, Bruno
experimental part, p. 8248 - 8255 (2011/01/09)
The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (p-PriC6H4Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) bridges, in the presence of a functionalised pyrenyl derivative (pyrene-R), affords the triangular prismatic host-guest compounds [(pyrene-R) ? Ru 6(p-PriC6H4Me)6(tpt) 2(dobq)3]6+ ([(pyrene-R) ? 1] 6+). The inclusion of eight mono-substituted pyrenyl derivatives including biologically relevant structures (a = 1-pyrenebutyric acid, b = 1-pyrenebutanol, c = 1-pyrenemethylamine, d = 1-pyrenemethylbutanoate, e = 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene, f = N-hexadecylpyrene-1-sulfonamide, g = pyrenyl ethacrynic amide and h = 2-(pyren-1-ylmethylcarbamoyl) phenyl acetate), and a di-substituted pyrenyl derivative (i = 1,8-bis(3-methyl-butyn-1- yl-3-ol)pyrene), has been accomplished. The carceplex nature of these systems with the pyrenyl moiety being firmly encapsulated in the hydrophobic cavity of the cage with the functional groups pointing outwards was confirmed by NMR (1H, 2D, DOSY) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 cancer cells. All the host-guest systems are more cytotoxic than the empty cage itself [1][CF3SO 3]6 (IC50 = 23 μM), the most active carceplex [f ? 1][CF3SO3]6 is an order of magnitude more cytotoxic.
Amide derivatives of ethacrynic acid: Synthesis and evaluation as antagonists of Wnt/β-catenin signaling and CLL cell survival
Jin, Guangyi,Lu, Desheng,Yao, Shiyin,Wu, Christina C.N.,Liu, Jerry X.,Carson, Dennis A.,Cottam, Howard B.
experimental part, p. 606 - 609 (2009/09/06)
A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range. Reduction of the α,β-unsatu
TRANSITION METAL COMPLEXES FOR INHIBITING RESISTANCE IN THE TREATMENT OF CANCER AND METASTASIS
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Page/Page column 20, (2008/06/13)
The present invention relates to organometallic compounds useful in the treatment of metastasis. The organometallic compounds comprise a ligand that is convalently bound to a bioactive compound, which is an inhibitor of a resistance pathway or a derivativ
