Quinolino[1,2-a]quinolinium bromide and isoquinolino[2,1-a]quinolinium bromide derivatives as DNA ligands and photocytotoxic agents

Abstract

Photopharmacology is one of the promising fields of research that allows activating various biochemical processes using light. This article describes the photoirradiation of styrylquinoline and styrylisoquinoline derivatives in aqueous solution and in MeCN resulting in the formation of the corresponding substituted quinolino[1,2-a]quinolinium or isoquinolino[2,1-a]quinolinium compounds. The obtained quinolinium derivatives bind to DNA by intercalation, whereas styrylquinoline and styrylisoquinoline form aggregates in DNA template as shown by photometric and fluorimetric titrations as well as by CD-spectroscopic analyses. The quinolinium ligands-DNA complexes can also be established in situ upon irradiation of styrylquinoline and styrylisoquinoline derivatives and the formation of intercalators directly in the presence of DNA. In addition to the DNA-binding properties, the tested quinolino[1,2-a]quinolinium and isoquinolino[2,1-a]quinolinium derivatives also operate as photosensitizers. They induce DNA damage at relatively low concentrations, even under anaerobic conditions, and therefore can be considered a potential platform for the development of type I PDT agents.