Complexes of lanthanides(iii) with mixed 2,2′-bipyridyl and 5,7-dibromo-8-quinolinoline chelating ligands as a new class of promising anti-cancer agents

Abstract

Five novel lanthanides(III) complexes, [Lu(Me)(MBrQ)₂NO₃] (MeMBrQ-Lu), [Ho(MeO)(MBrQ)₂NO₃] (MeOMBrQ-Ho), [Ho(Me)(MBrQ)₂NO₃] (MeMBrQ-Ho), [La(Me)₂(BrQ)₂NO₃] (MeBrQ-La) and [Sm(Me)(BrQ)₂(CH₃OH)NO₃] (MeBrQ-Sm), have been synthesized, in which 2,2′-bipyridyl (4,4′-dimethyl-2,2′-bipyridyl (Me) and 4,4′-dimethoxy-2,2′-bipyridine (MeO)) and 5,7-dibromo-8-quinolinoline derivatives (5,7-dibromo-2-methyl-8-quinolinol (MBrQ-H) and 5,7-dibromo-8-quinolinol (BrQ-H)) act as the chelating ligands. The in vitro cytotoxic activities of the five Ln(III) complexes have been studied with the SK-OV-3/DDP, NCI-H460 and HeLa cancer cells. MeMBrQ-Lu, MeOMBrQ-Ho, MeMBrQ-Ho, MeBrQ-La and MeBrQ-Sm show higher cytotoxicity against the HeLa cells (IC₅₀ values of 1.00 nM–3.45 μM) than cisplatin (13.11 ± 0.53 μM). In particular, the MeOMBrQ-Ho and MeMBrQ-Ho complexes exhibit superior cytotoxic activity, with IC₅₀ values at 1.00 ± 0.34 nM and 125.00 ± 1.08 nM. We further demonstrate that MeOMBrQ-Ho and MeMBrQ-Ho inhibit the proliferation of HeLa cells by inhibiting telomerase and targeting mitochondria to induce DNA damage-mediated apoptosis. In addition, MeOMBrQ-Ho significantly inhibits tumor growth with a tumor growth inhibition rate (IR) of 50.8% in a HeLa mouse xenograft model. Taken together, MeOMBrQ-Ho is a novel lanthanide(III) complex with promising antitumor activity.