Anticancer metallohelices: Nanomolar potency and high selectivity

Rebecca A. Kaner, Simon J. Allison, Alan D. Faulkner, Roger M. Phillips, David I. Roper, Samantha L. Shepherd, Daniel H. Simpson, Nicholas R. Waterfield, Peter Scott

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)951-958
Number of pages8
JournalChemical Science
Issue number2
Early online date26 Oct 2015
Publication statusPublished - 1 Feb 2016


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