Photochemical, photophysical and photobiological properties of some methylallopsoralens which are potential agents for photochemotherapy

• Published in: Biochimica et biophysica acta Vol. 925; no. 2; pp. 101 - 108
• Main Authors: Vedaldi, Daniela, Dall'Acqua, Francesco, Guiotto, Adriano, Caffieri, Sergio, Baccichetti, Francarosa, Knox, Caroline N., George Truscott, T., Land, Edward J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.08.1987; Elsevier; North-Holland
• Subjects: Benzene; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Cross-Linking Reagents; DNA - biosynthesis; DNA photobinding; Free Radicals; Furocoumarins - radiation effects; General pharmacology; Medical sciences; Methylallopsoralen; Oxygen; Pharmacology. Drug treatments; Photochemistry; Photochemotherapy; Physicochemical properties. Structure-activity relationships; PUVA Therapy - methods; RNA - biosynthesis; Singlet oxygen; T-Phages - genetics; Water; 4,7,4′-TMAP, 4,7,4′-trimethylallopsoralen; Singlet oxygen; 1 O 2 ∗ , singlet oxygen; DNA photobinding; Methylallopsoralen; Photochemotherapy; RNO, p-nitrosodimethylaniline; 4,7-DMAP, 4,7-dimethylallopsoralen; 4,7,5′-TMAP, 4,7,5′-trimethylallopsoralv 8-MOP, 8-methoxypsoralen; Molecular interaction; Photochemical reaction; Structure activity relation; Photoactivation; DNA; Phototherapy
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(87)90098-5

Two new trimethylallopsoralens, 4,7,4′- and 4,7,5′-trimethylallopsoralen, form molecular complexes with DNA and by successive UVA (320–400 nm) irradiation photobind monofunctionally to the macromolecule. The DNA photobinding rates at 365 nm and photobinding quantum yields at 330 nm are markedly higher for 4,7,4′-trimethylallopsoralen than for 4,7,5′-trimethylallopsoralen. Their capacities to generate singlet oxygen in water and benzene are low, particularly for 4,7,4′-trimethylallopsoralen, and the two trimethylallopsoralens completely lack skin phototoxicity on guinea-pig skin. Both compounds show antiproliferative activity in terms of DNA synthesis inhibition in Ehrlich cells and T 2 phage infectivity higher than that displayed by angelicin. In view of its monofunctional character, lack of skin phototoxicity, low singlet oxygen yield and antiproliferative activity, 4,7,4′-trimethylallopsoralen deserves further clinical studies as a potential photochemotherapeutic agent.