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Synthesis and biological evaluation of substituted 3-(2'-benzimidazolyl)coumarin platinum(II) complexes as new telomerase inhibitors.
Journal of Inorganic Biochemistry 2018 September 25
Eight new platinum(II) complexes Pt1-Pt8 with substituted 3‑(2'‑benzimidazolyl) coumarins were successfully synthesized and characterized by single crystal X-ray diffraction analysis, nuclear magnetic resonance spectroscopy (NMR), electrospray ionization-mass spectrometry (ESI-MS), infrared spectrophotometry (IR) and elemental analysis. Crystallographic data of these Pt1-Pt8 complexes showed that the Pt(II) has distorted four-coordinated square planar geometry. Pt1-Pt8 were found to display high cytotoxic activity in vitro against the cisplatin-resistant SK-OV-3/DDP cancer cells with a low IC50 from 1.01-10.32 μM, but low cytotoxicity on the normal HL-7702 cells. Further studies revealed that Pt1-Pt3 induced apoptosis in SK-OV-3/DDP cancer cells via mitochondria dysfunction signaling pathways. Our findings also indicated that Pt1 was a telomerase inhibitor targeting c-myc promoter elements.
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