Gold amides as anticancer drugs: synthesis and activity studies

Article English OPEN
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
  • Related identifiers: doi: 10.1039/C3OB27460H
  • Subject: 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.
  • References (24)
    24 references, page 1 of 3

    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.

  • Related Research Results (1)
  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    87
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Sussex Research Online - IRUS-UK 0 87
Share - Bookmark