LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Newcombe, Sonya; Bobin, Mariusz; Shrikhande, Amruta; Gallop, Chris; Pace, Yannick; Yong, Helen; Gates, Rebecca; Chaudhuri, Shuvashri; Roe, Mark; Hoffmann, Eva; Viseux, Eddy M E (2013)
Publisher: Royal Society of Chemistry
Languages: English
Types: Article
Subjects: RC0254, Q, RM0300, QD, RD0651, RM0671, RS0400, QD0241, QD0146
Modular gold amide chemotherapeutics: Access to modern chemotherapeutics with robust and flexible synthetic routes that are amenable to extensive customisation is a key requirement in drug synthesis and discovery. A class of chiral gold amide complexes featuring amino acid derived ligands is reported herein. They all exhibit in vitro cytotoxicity against two slow growing breast cancer cell lines with limited toxicity towards normal epithelial cells.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1 C. Orvig and M. J. Abrams, Medicinal inorganic chemistry: introduction, Chem. Rev., 1999, 99, 2201-2204.
    • 2 M. Patra and G. Gasser, Organometallic compounds: an Fig. 6 TrxR activity in vitro is inhibited by gold(I) complexes. Increasing concen- opportunity for chemical biology?, ChemBioChem, 2012, 13, trations of complexes 1 and 2 or 'ligand only' were added to TrxR and GR 1232-1252.
    • enzymes and their activity was monitored by fluorescence. Normalized fluor- 3 I. Ott and R. Gust, Non platinum metal complexes as antiescence values were calculated by taking the fluorescence value of the treated cancer drugs, Arch. Pharm., 2007, 340, 117-126.
    • twreealltmanedntd).ividing it by the fluorescence value of 0 nM compound (DMSO-only 4 M. Stallings-Mann, L. Jamieson, R. P. Regala, C. Weems, N. R. Murray and A. P. Fields, A novel small-molecule inhibitor of protein kinase Ciota blocks transformed complexes, and were shown to have no cytotoxic effects on growth of non-small-cell lung cancer cells, Cancer Res., their own. We have also demonstrated the compatibility of a 2006, 66, 1767-1774.
    • wide array of functionalities such as indoles, phenol triflates, 5 J. L. Hickey, R. A. Ruhayel, P. J. Barnard, M. V. Baker, esters, methyl sulfide, amides, aliphatic chains, aromatic S. J. Berners-Price and A. Filipovska, Mitochondria-targeted groups, diarylalkyl- and triaryl-phosphines. An alternative chemotherapeutics: the rational design of gold(I) N-heterochemical environment that was equally active as the gold triflic cyclic carbene complexes that are selectively toxic to cancer amide complexes was also validated. The use of a zwitterionic cells and target protein selenols in preference to thiols, ligand bearing a delocalised cation clearly sets a precedent for J. Am. Chem. Soc., 2008, 130, 12570-12571.
    • the use of therapeutically active analogues of globally electro- 6 C. Wetzel, P. C. Kunz, M. U. Kassack, A. Hamacher, neutral pyridinium gold(I) complexes in treating cancer. The P. Bohler, W. Watjen, I. Ott, R. Rubbiani and B. Spingler, two approaches described herein open up new possibilities for Gold(I) complexes of water-soluble diphos-type ligands: synan increased diversity in new chemotypes and prodrug deliv- thesis, anticancer activity, apoptosis and thioredoxin ery, including peptoid and peptidic precursors as well as reductase inhibition, Dalton Trans., 2011, 40, 9212-9220.
    • orthogonal anticancer drugs. 7 J. C. Lima and L. Rodriguez, Phosphine-gold(I) compounds The selective accumulation of the gold(I) complexes in as anticancer agents: general description and mechanisms adenocarcinoma cells due to their mitochondrial hyperpolariz- of action, Anti-Cancer Agents Med. Chem., 2011, 11, 921-928.
    • ation may provide a favourable therapeutic index for the treat- 8 C. Gabbiani and L. Messori, Protein targets for anticancer ment of tumours. This opens up the possibility of targeting gold compounds: mechanistic inferences, Anti-Cancer cancers in elderly patients and of slow-growing tumours, Agents Med. Chem., 2011, 11, 929-939.
    • where the conventional cancer therapeutics aimed at rapidly 9 S. P. Fricker, Strategies for the biological evaluation of gold dividing cells cannot be used. anticancer agents, Anti-Cancer Agents Med. Chem., 2011, 11, 940-952.
    • 10 X. Zhang, M. Frezza, V. Milacic, L. Ronconi, Y. Fan, C. Bi, Funding sources D. Fregona and Q. P. Dou, Inhibition of tumor proteasome activity by gold-dithiocarbamato complexes via both redoxE.H. is the recipient of an MRC Senior Fellowship and EMBO dependent and -independent processes, J. Cell. Biochem., Young Investigator Award. E.M.E.V. is funded by an Alfred 2010, 109, 162-172.
    • Bader award. 11 K. Yan, C. N. Lok, K. Bierla and C. M. Che, Gold(I) complex of N,N′-disubstituted cyclic thiourea with in vitro and in vivo anticancer properties-potent tight-binding inhiAcknowledgements bition of thioredoxin reductase, Chem. Commun., 2010, 46, 7691-7693.
    • We thank Dr Iain Day for the NMR service and Dr Alaa Abdul- 12 C. X. Zhang and S. J. Lippard, New metal complexes as Sada for the Mass Spectrometry Service at the University of potential therapeutics, Curr. Opin. Chem. Biol., 2003, 7, Sussex; the NCS at Southampton for X-ray data for compound 481-489.
    • 13 N. Mezailles, L. Ricard and F. Gagosz, Phosphine gold(I) bis-(trifluoromethanesulfonyl)imidate complexes as new highly efficient and air-stable catalysts for the cycloisomerization of enynes, Org. Lett., 2005, 7, 4133-4136.
    • 14 T. Amagai, T. K. Miyamoto, H. Ichida and Y. Sasaki, Preparation and crystal-structure of new gold(I) complexes linked to pyrimidines, Bull. Chem. Soc. Jpn., 1989, 62, 1078-1080.
    • 15 J. Lemke, A. Pinto, P. Niehoff, V. Vasylyeva and N. MetzlerNolte, Synthesis, structural characterisation and anti-proliferative activity of NHC gold amino acid and peptide conjugates, Dalton Trans., 2009, 7063-7070.
    • 16 A. Thaqi, J. L. Scott, J. Gilbert, J. A. Sakoff and A. McCluskey, Synthesis and biological activity of delta-5,6- norcantharimides: importance of the 5,6-bridge, Eur. J. Med. Chem., 2010, 45, 1717-1723.
    • 17 L. B. Chen, Mitochondrial membrane potential in living cells, Annu. Rev. Cell Biol., 1988, 4, 155-181.
    • 18 J. S. Modica-Napolitano, R. Nalbandian, M. E. Kidd, A. Nalbandian and C. C. Nguyen, The selective in vitro cytotoxicity of carcinoma cells by AZT is enhanced by concurrent treatment with delocalized lipophilic cations, Cancer Lett., 2003, 198, 59-68.
    • 19 D. T. Hill, A. A. Isab, D. E. Griswold, M. J. DiMartino, E. D. Matz, A. L. Figueroa, J. E. Wawro, C. DeBrosse, W. M. Reiff, R. C. Elder, B. Jones, J. W. Webb and C. F. Shaw, Seleno-auranofin (Et3PAuSe-tagl): synthesis, spectroscopic (EXAFS, 197Au Mossbauer, 31P, 1H, 13C, and 77Se NMR, ESI-MS) characterization, biological activity, and rapid serum albumin-induced triethylphosphine oxide generation, Inorg. Chem., 2010, 49, 7663-7675.
    • 20 D. T. Poole, T. C. Butler and M. E. Williams, The effects of nigericin, valinomycin, and 2,4-dinitrophenol on intracellular pH, glycolysis, and K + concentration of Ehrlich ascites tumor cells, Biochim. Biophys. Acta, 1972, 266, 463-470.
    • 21 S. Davis, M. J. Weiss, J. R. Wong, T. J. Lampidis and L. B. Chen, Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells, J. Biol. Chem., 1985, 260, 13844-13850.
    • 22 A. G. Cox, K. K. Brown, E. S. Arner and M. B. Hampton, The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation, Biochem. Pharmacol., 2008, 76, 1097-1109.
    • 23 Y. Omata, M. Folan, M. Shaw, R. L. Messer, P. E. Lockwood, D. Hobbs, S. Bouillaguet, H. Sano, J. B. Lewis and J. C. Wataha, Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1), Toxicol. in Vitro, 2006, 20, 882-890.
    • 24 M. Bjornstedt, S. Kumar, L. Bjorkhem, G. Spyrou and A. Holmgren, Selenium and the thioredoxin and glutaredoxin systems, Biomed. Environ. Sci., 1997, 10, 271-279.
  • No similar publications.

Share - Bookmark

Cite this article