Photochemical and photobiological studies on furoquinazolines as new psoralen analogs

[Display omitted] •New linear and angular furoquinazolines (FQZs) were synthesized and studied.•After intercalation, the two FQZs did not photoreact with DNA under UVA light.•FQZs induced an oxidative DNA damage under UVA irradiation.•The production of ROS was responsible for the photosensitizing properties of FQZs.•Flash photolysis studies confirmed the photooxidizing properties on biological substrates. Linear (L) and angular (A) 4′,5′-dimethylfuroquinazolines (FQZs) were synthesized and studied as furocoumarin analogs. These molecules proved to be photounstable with a photodegradation extent correlated to UVA light doses. Both compounds did intercalate inside the DNA double helix, but were not able to photobind DNA bases under UVA irradiation. This behavior was further rationalized through docking studies. The photosensitizing effects of these compounds were evaluated on Jurkat tumor cells and NCTC-2544 human keratinocytes, with and without antioxidants, to demonstrate the involvement of a photodynamic mechanism. Indeed, significant amounts of singlet oxygen and superoxide anion were generated in the presence of both compounds, that account for the oxidative damage induced to some isolated biological substrates (DNA, amino acids, proteins and lipids). Photophysical studies by use of a flash photolysis set up showed detectable triplet population and production of singlet reactive oxygen species for linear furoquinazoline, which can be responsible for the oxidation of biological substrates, and therefore can affect the cell proliferation.