Synthesis, cytotoxic evaluation and DNA binding study of 9-fluoro-6H-indolo[2,3-b]quinoxaline derivatives

Abstract

A series of novel 9-fluoro-6H-indolo[2,3-b]quinoxaline derivatives as antitumor agents were synthesized and studied. The designed compounds feature positive charges both at the 11-N position of the aromatic scaffold and the side-chain alkylamino group. The corresponding in vitro antitumor activities were evaluated against MCF-7, HeLa and A549 cancer cell lines and the DNA binding properties of these compounds were characterized by UV-vis, fluorescence, and circular dichroism (CD) spectroscopy as well as thermal denaturation. The obtained results indicate that the dicationic quaternary ammonium salt derivatives of 9-fluoro-6H-indolo[2,3-b]quinoxaline may serve as intercalators with increased DNA binding affinity. Furthermore, both the incorporation of fluorine, and alkyl amino side chains and the introduction of a positive charge at the 11-N position of the aromatic scaffold was shown to be responsible for their antitumor activity and improved DNA binding ability. Taken in concert, these findings may be valuable in the understanding of the antitumor effect of these compounds and may further provide important information for the future optimization of the DNA binding properties of this drug type.