Photo-activated DNA binding and antimicrobial activities of Furoquinoline and Pyranoquinolone alkaloids from Rutaceae

To find novel photo-active compounds of potential use in photochemotherapy from higher plants, photo-activated antimicrobial and DNA binding activities of the furoquinolines, skimmianine, kokusagimine, and haplopine, and a pyranoquinolone, flindersine, from two species of Rutaceae plants were investigated. TLC overlay assays against a methichillin-resistant strain of Staphylococcus aureus and Candida albicans were employed to test antimicrobial properties. All of the tested compounds showed photo-activated antimicrobial activity against S. aureus in the order of kokusaginine > haplopine, flindersine > skimmianine. Weaker activity was found for C. albicans. Photo-activated DNA binding activity of these compounds was investigated by a method using restriction enzymes and a specially designed 1.5 kb DNA fragment. Kokusaginine showed inhibition against all of the 46 restriction enzymes. Haplopine showed a similar inhibition pattern but the binding activity against AscI and Sma I with restriction sequences consisting only of G and C was very weak. Skimmianine showed binding activity against Xba I, BciV I, Sal I, Pst I, Sph I and Hind III, but very weak or no activity was found for the other restriction enzymes. A pyranoquinolone, flindersine, showed no activity against any of the restriction enzymes. Photo-activated DNA binding activity of furoquinolines was therefore in the order of kokusaginine > haplopine > skimmianine, which was the same order as their photo-activated antimicrobial activity against S. aureus. Therefore, it was concluded that DNA is one of the cellular targets for the furoquinolines to exert their biological activities, similar to psoralens. However, because flindersine showed photo-activated antimicrobial activity against S. aureus but did not show photo-activated DNA binding activity, it is clear that there are other cellular target components for this compound to exert photo-toxic activity.