Monosaccharides are added to the hydrophilic face of a self-assembled asymmetric FeII metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water-stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53+/+ ) with respect to the non-cancerous ARPE-19 cell line. While the most selective compound is a glucose-appended enantiomer, its cellular entry is not mainly glucose transporter-mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5-fold, and a non-destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects.

Department of Biophysics Centre of the Region Hana for Biotechnological and Agricultural Research Faculty of Science Palacký University Šlechtitelů 27 78371 Olomouc Czech Republic

Department of Chemistry University of Warwick Coventry CV4 7AL UK

School of Applied Sciences University of Huddersfield Huddersfield HD1 3DH UK

The Czech Academy of Sciences Institute of Biophysics Kralovopolska 135 61265 Brno Czech Republic

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Dicobalt(ii) helices kill colon cancer cells via enantiomer-specific mechanisms; DNA damage or microtubule disruption