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Anticancer metallohelices : nanomolar potency and high selectivity
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Kaner, Rebecca A., Allison, Simon A., Faulkner, Alan D., Simpson, Daniel H., Waterfield, Nicholas R., Phillips, Roger M., Roper, David I., Shepherd, Samantha L. and Scott, Peter (2016) Anticancer metallohelices : nanomolar potency and high selectivity. Chemical Science, 7 (2). pp. 951-958. doi:10.1039/c5sc03677a ISSN 2041-6520.
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Official URL: http://dx.doi.org/10.1039/C5SC03677A
Abstract
A range of new helicate-like architectures have been prepared via highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [Fe2L3]Cl4.nH2O (L = various bidentate ditopic ligands NN–NN) show very good water solubility and stability. Their activity against a range of cancer cell lines in vitro is structure-dependent and gives IC50 values as low as 40 nM. In an isogenic pair of HCT116 colorectal cancer cells, preferential activity was observed against cell lines that lack functional p53. Selectivity is also excellent, and against healthy human retinal pigment epithelial (ARPE19) and lung fibroblast (WI38) cells IC50 values are nearly three orders of magnitude higher. Cisplatin is unselective in the same tests. The compounds also appear to have low general toxicity in a number of models: there is little if any antimicrobial activity against Methicillin-resistant Staphylococcus aureus and Escherichia coli.; Acanthamoeba polyphaga is unaffected at 25 μg ml -1 (12.5 μM); Manduca sexta larvae showed clear evidence of systemic distribution of the drug, and rather than any observation of adverse effects they exhibited a significant mean weight gain vs controls. Investigation of the mode of action revealed no significant interaction of the molecules with DNA, and stimulation of substantial cell death by apoptosis.
Item Type: | Journal Article | ||||||||||
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Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Metal complexes -- Therapeutic use | ||||||||||
Journal or Publication Title: | Chemical Science | ||||||||||
Publisher: | Royal Society of Chemistry | ||||||||||
ISSN: | 2041-6520 | ||||||||||
Official Date: | February 2016 | ||||||||||
Dates: |
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Volume: | 7 | ||||||||||
Number: | 2 | ||||||||||
Number of Pages: | 9 | ||||||||||
Page Range: | pp. 951-958 | ||||||||||
DOI: | 10.1039/c5sc03677a | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
Date of first compliant deposit: | 30 March 2016 | ||||||||||
Date of first compliant Open Access: | 30 March 2016 | ||||||||||
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