PYRROLOQUINOLINONE METHYLDERIVATIVES, FUROCOUMARIN ANALOGS - INTERACTION WITH BIOMOLECULES AND COMPUTER-AIDED STUDIES

Pyrroloquinolinones, furocoumarin analogues, contain a divinilbenzene moiety, suggesting possible photoreactivity. Quantum mechanics calcula tions indicate that the pyrrole-side double bond exhibits strong photo reactivity, while the pyridone-side double bond is only poorly photore active. Intercalation models obtained by molecular mechanics calculati ons suggest that, in the cis-syn intercalation arrangement, the pyrido ne-side double bond is well aligned with the nearby thymine, supportin g possible C-4-cycloaddition with the 5,6 double bond of thymine, whil e the pyrrole-side double bond assumes an unfavourable position for ph otobinding. These data suggest that photoreaction between the pyridone -side and thymine double bonds may takes place, although with very low yield. Experimental evidence concerning DNA-photobinding exhibited by 2,6-dimethyl-9-methoxy-4H-pyrroloquinolinone (Compound I) confirms th eoretical predictions. The formation of C-4- cycloadducts between the pyridone side double bond and thymine also takes place with very low y ield. Compound I shows marked BSA photobinding, suggesting that pyrrol oquinolinones may photoreact with proteins. The three pyrroloquinolino nes examined show high yields of singlet oxygen generation, suggesting that photobiological effects may be obtained through this photodynami c pathway, rather than through DNA photobinding.