MONOFUNCTIONAL COVALENT PHOTOBINDING OF DICTAMNINE, A FUROQUINOLINE ALKALOID, TO DNA AS TARGET IN VITRO

Abstract— The naturally occurring furoquinoline alkaloid, dictamnine, is phototoxic to Gram-positive bacteria, yeasts and filamentous fungi in the presence of long-wave UV light. Prior to photobinding to DNA dictamnine forms a complex with the macromolecule in the dark. Photobinding to DNA is shown with [³H]-dictamnine. In contradiction to an earlier finding, dictamnine proved to be incapable of forming interstrand crossiinkages with native DNA. This fact was ascertained by the use of methods additional to hydroxyapatite column chromatography, e.g. alkaline sucrose gradient centrifugation and hyperchromicity tests. The alkaloid therefore represents a new monofunctional photoreagent towards DNA in vitro. It is assumed that it binds through its furyl-C=C to DNA. The inability to form crosslinks may be attributed to the stability of the lateral aromatic nucleus. As no photoreactivity against human erythrocytes could be observed, it is possible that nucleic acids represent the major target of damage in vivo.