Linking of Antitumor trans NHC-Pt(II) Complexes to G-Quadruplex DNA Ligand for Telomeric Targeting

摘要: G-quadruplex structures (G4) are promising anticancerous targets. A great number of small molecules targeting these have already been identified through biophysical methods. In cellulo, some them able to target either telomeric DNA and/or sequences involved in oncogene promotors, both resulting cancer cell death. However, only a few bind G4 irreversibly. Here we combine within the same molecule G4-binding agent PDC (pyridodicarboxamide) with N-heterocyclic carbene-platinum complex NHC-Pt for its antitumor properties. The conjugate platinum NHC-Pt-PDC stabilizes strongly vitro, affinity slightly affected as compared PDC. addition, show that new binds preferentially and irreversibly quadruplex form human sequence profile way different from thereby indicating platination reaction is oriented by stacking moiety onto G4-structure. induces significant loss TRF2 telomeres considerably more important than effect two components alone, NHC-Pt, respectively.