Increased activity of the enzyme telomerase prevents apoptosis (cell death) by extending DNA by the addition of a telomere (TTAGGG). Telomerase is present in 85% of cancer cells. Inhibition of telomerase can be affected through the stabilization of G-quadruplexes formed through Hoogsteen base pairing in guanine-rich areas of the telomere. G-quadruplexes can be stabilized through p-p stacking therefore square-planar transition-metal complexes with conjugated ligands are target molecules for inhibitors. The addition of partially-positive or fully-positive pendant groups to the ligand can interact with the negatively charged phospodiester backbone of the telomere thus creating increased stabilization. A known nickel (II) salen complex with a piperidine pendant group was synthesized and was analyzed for telomerase inhibition using the TRAP assay. The syntheses of salen complexes with pendant groups containing trimethylammonium and methylimidazolium were unsuccessful. We are currently synthesizing a series of platinum (II) terpyridine complexes following the established synthesis with a piperidine pendant group. The novel syntheses of terpyridine complexes with pendant groups derived from arginine and lysine are being synthesized. The degree of telomerase inhibition for each synthesized molecule is assessed using the TRAP assay on myeloma cells.

Synthesis of platinum (II) terpyridine complexes with the capability to stabilize the G-quadruplex and inhibit telomerase activity

247th National Meeting (2014)

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