【文章名】5-N-Methylated Quindoline Derivatives as Telomeric G-Quadruplex Stabilizing Ligands: Effects of 5-N Positive Charge on Quadruplex Binding Affinity and Cell Proliferation.
5-N-Methylated Quindoline Derivatives as Telomeric G-Quadruplex Stabilizing Ligands: Effects of 5-N Positive Charge on Quadruplex Binding Affinity and Cell Proliferation.
[摘要]：A series of 5-N-Me quindoline (cryptolepine) derivs. as telomeric quadruplex ligands was synthesized and evaluated. The designed ligands possess a pos. charge at the 5-N position of the arom. quindoline scaffold. The quadruplex binding of these compds. was evaluated by CD (CD) spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, NMR (NMR), and mol. modeling studies. Introduction of a pos. charge not only significantly improved the binding ability but also induced the selectivity toward antiparallel quadruplex, whereas the nonmethylated derivs. tended to stabilize hybrid-type quadruplexes. NMR and mol. modeling studies revealed that the ligands stacked on the external G-quartets and the pos. charged 5-N atom could contribute to the stabilizing ability. Long-term exposure of human cancer cells to I showed a remarkable cessation in population growth and cellular senescence phenotype and accompanied by a shortening of the telomere length.
