Pyridostatins selectively recognize two different forms of the human telomeric G-quadruplex structures and their anti-tumor activities in vitro

Abstract

G-quadruplex as a therapeutic target to develop novel anti-cancer agents has attracted a growing interest. Among all the ligands of G-quadruplexes, pyridostatin derivatives play a very important role. Here, we first reported the recognition of the fundamental skeleton pyridostatin I, which was simply synthesized. Compared to pyridostatin II comprising terminal amino groups, pyridostatin I selectively stabilized intramolecular anti-parallel telomeric G-quadruplex by raising the melting temperature about 20 °C at 295 nm of H22, while pyridostatin II preferred to stabilize intermolecular parallel telomeric G-quadruplex by raising the melting temperature about 25 °C at 265 nm of H7, maybe due to the suited size measurements between G-quadruplex hosts and pyridostatin guests. MTT assays indicated that pyridostatin II had better cytotoxic effects against HCT-8 and A549 cell lines obviously, indicating positively charged side chains may be required for improving the water solubility and cellular uptake of the apolar central skeleton.