alexa In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines.
Pharmaceutical Sciences

Pharmaceutical Sciences

Biochemistry & Pharmacology: Open Access

Author(s): Deegan C, Coyle B, McCann M, Devereux M, Egan DA

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Abstract The anti-cancer chemotherapeutic potential of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)(3)](ClO(4))(2).4H(2)O and [Ag(phendione)(2)]ClO(4) were determined using four human cells lines, i.e. two neoplastic (A-498 and Hep-G2) and two non-neoplastic (CHANG and HK-2). All of the phendione derivatives induced a concentration-dependant decrease in the viability of the four cell lines, with [Cu(phendione)(3)](ClO(4))(2).4H(2)O displaying greatest activity. In comparative studies, IC(50) values obtained with the two neoplastic cell lines showed a cytotoxic response which was between 3 and 35 times greater than that observed for the metal-based anti-cancer agent, cisplatin. Furthermore, metal-phendione complexes, rather than simple solvated metal ions, were responsible for the observed cytotoxicity. Despite the high level of potency associated with these compounds they did not display an apparent cyto-selective profile, as they reduced the viability of both neoplastic and non-neoplastic cells. However, selected mechanistic studies showed that phendione and its metal complexes inhibited DNA synthesis which did not appear to be mediated through intercalation. Ames testing highlighted that all three compounds and their phase I metabolites were non-mutagenic, unlike cisplatin. Taken together, these results suggest that phendione and its Cu(II) and Ag(I) complexes may be capable of acting as highly effective anti-cancer therapies, which with careful administration could provide very potent and effective alternatives to cisplatin. This article was published in Chem Biol Interact and referenced in Biochemistry & Pharmacology: Open Access

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