Effect of molecular structure on the photophysical properties, the photoreactivity with DNA and the photobiological activity of monofunctional pyridopsoralens

— 7-Methyl-pyrido[4,3-c]psoralen (2N-MePyPs) has been synthesized in order to investigate the possible effect of the position of the pyridine-nitrogen atom on the photoreactivity towards DNA and the photobiological activity of pyridopsoralens, a new family of psoralen derivatives. In comparison to its isomer, 7-methyl-pyrido[3,4-c]psoralen (MePyPs), 2N-MePyPs shows a 2.5 times lower DNA photobinding capacity. Photobiological experiments with diploid yeast (Saccharomyces cerevisiae) reveal that this compound differs strikingly from its isomer MePyPs. It has only a weak antiproliferative potential and, per unit dose, a lower capacity than MePyPs for the induction of nuclear genotoxic effects. With respect to these latter features, 2N-MePyPs resembles the monofunctional furocoumarin 3-CPs.