Ruthenium(ii) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase?

Dalton Transactions Pub Date: 2015-01-07 DOI: 10.1039/C4DT03585B

Abstract

One novel ruthenium polypyridyl complex, [Ru(bpy)2(icip)]2+ (1), and two previously reported ruthenium polypyridyl complexes, [Ru(bpy)2(pdppz)]2+ (2) and [Ru(bpy)2(tactp)]2+ (3) (bpy = 2,2′-bipyridine, icip = 2-(indeno[2,1-b]chromen-6-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, pdppz = phenanthro[4,5-abc]dipyrido[3,2-h:2′,3′-j]phenazine, tactp = 4,5,9,18-tetraazachryseno[9,10-b]-triphenylene), have been synthesised. As expected, these complexes show inhibition towards telomerase by inducing and stabilising the G-quadruplex structure, and behave as topoisomerase I/II poisons at the same time. Additionally, the acute and chronic cytotoxicities of the complexes are considered. Furthermore, cell apoptosis experiments are used to briefly study the mechanism. Because studies involving multi-target inhibition towards topoisomerase and telomerase of Ru(II) complexes have not been reported previously, the present research may help to develop innovative chemical strategies and therapies.

Graphical abstract: Ruthenium(ii) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase
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