Anticancer metallohelices: nanomolar potency and high selectivity.

A range of new helicate-like architectures have been prepared highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [FeL]Cl·HO (L = various bidentate ditopic ligands NN-NN) show very good water solubility and stability. Their activity against a range of cancer cell lines is structure-dependent and gives IC 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 IC 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 and ; is unaffected at 25 μg mL (12.5 μM); 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 controls. Investigation of the mode of action revealed no significant interaction of the molecules with DNA, and stimulation of substantial cell death by apoptosis.