Synthesis, DNA binding and biological activity of oxazolopyridocarbazole-netropsin hybrid molecules

Abstract

A series of bifunctional molecules have been synthesized which result from the combination of a DNA sequence-specific ligand (netropsin) coupled to an intercalator moiety (OPC). The binding constants to double-stranded polynucleotides as well as the cytostatic activity against both murine and human tumor cell lines and the in vitro activity against a range of DNA and RNA viruses (including human immunodeficiency virus) have been determined for these novel molecules. All of them retain the DNA binding affinity of netropsin but with a notable decrease of A–T sequence selectivity. They did not show in vitro antiviral activity. On the other hand, these compounds demonstrated enhanced cytostatic activity against both human and murine tumor cell lines.