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Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function.
MedChemComm 2018 October 2
Four new platinum(ii) complexes, [Pt(Rut)(DMSO)Cl2 ] ( Rut-Pt ), [Pt(Try)(DMSO)Cl2 ] ( Try-Pt ), [Pt(ITry)(DMSO)Cl2 ] ( ITry-Pt ) and [Pt(BrTry)(DMSO)Cl2 ] ( BrTry-Pt ), with rutaecarpine (Rut), tryptanthrin (Try), 8-iodine-tryptanthrin (ITry) and 8-bromo-tryptanthrin (BrTry) as ligands were synthesized and fully characterized. In these complexes, the platinum(ii) adopts a four-coordinated square planar geometry. The inhibitory activity evaluated by the MTT assay showed that BrTry-Pt (IC50 = of 0.21 ± 0.25 μM) could inhibit the growth of T-24 tumor cells (human bladder cancer cell line) more so than the other three complexes. In addition, all of these Pt complexes exhibited low toxicity against non-cancerous HL-7702 cells. BrTry-Pt induced cell cycle arrest in the S phase, leading to the down-regulation of cyclin A and CDK2 proteins. BrTry-Pt acts as a telomerase inhibitor targeting the c-myc promoter. In addition, BrTry-Pt also caused mitochondrial dysfunction. Importantly, the in vitro anticancer activity of BrTry-Pt was higher than those of Rut-Pt , Try-Pt and ITry-Pt , and it was more selective for T-24 cells than for non-cancerous HL-7702 cells.
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