Biophysical and biological properties of newly synthesized dioxinocoumarin derivatives. Part I: Dark effects on T7 phage and HeLa cells

Abstract

Several dioxinocoumarin derivatives have been synthesized for photochemotherapeutical purposes. The physicochemical properties of 3,4-benzo-6,7-dioxinocoumarin and its biological activity in the dark were studied with regard to future photobiological applications. It was found that molecular aggregates are formed in aqueous solution at a concentration higher than 10(-5) mol l-1. In the dark, 3,4-benzo-6,7-dioxinocoumarin inactivates T7 phage and inhibits the growth of HeLa cells in a concentration-dependent manner. The dark inactivation of T7 phage was quantitatively characterized. It was found to be higher than that of 8-methoxypsoralen (8-MOP) and approximately equal to 4,6,4'-trimethylangelicin (TMA). From the inactivation kinetics and the lack of a quenching effect of polynucleotides on the fluorescence emission of the drug, it appears that, apart from the induction of DNA damage, other events are implicated in T7 phage dark inactivation. These results are important for the interpretation of the photobiological effects of this type of compound.