3-Alkyl- and 3-aryl-7H-furo[3,2-g]-1-benzopyran-7-ones: synthesis, photoreactivity, and fluorescence properties.
A series of 3-alkyl- and 3-aryl-7H-furo[3, 2-g]-1-benzopyran-7-ones, known as linear furocoumarins, was synthesized and evaluated for their dark- and photobinding (crosslink formation) with DNA as well as for their spectrophotometric and fluorescent properties, lipophilicity, and ability to photobleach N, N-dimethyl-p-nitrosoaniline (RNO) after irradiation with UVA light. 8-Methoxypsoralen (8-MOP, 9-methoxy-7H-furo[3, 2-g]-1-benzopyran-7-one) and 4, 5', 8-trimethylpsoralen (TMP, 2, 5, 9-trimethyl-7H-furo[3, 2-g]-1-benzopyran-7-one) were used as reference compounds in all tests. The investigations support the formation of a molecular complex between the furocoumarins and DNA. Crosslink formation with DNA after irradiation with UVA light was detectable for compounds with a methyl or phenyl substituent in position 3, but not for those bearing either a tert-butyl, a 4-methoxyphenyl, or a 2, 5-dimethoxyphenyl group. All furocoumarins exhibited sufficient absorption in the UVA wavelength range and are fluorescent. All compounds showed a higher lipophilicity than 8-MOP. Generally the 3-alkyl substituted furocoumarins had a capacity to photobleach RNOwhich was higher than that of the 3-aryl substituted ones. Some of the 3-aryl substituted furocoumarins displayed a photobleaching ability which was similar to or lower than that of 8-MOP.
Körner
Paul
P
Pharmazeutisches Institut, Universität Kiel, Germany. pKoerner@pharmazie.uni-kiel.de
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts; D005453:Fluorescence; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000737:chemistry; D011701:PUVA Therapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D018736:DNA Adducts; D011564:Furocoumarins; D017319:Photosensitizing Agents; D004247:DNA; C427203:calf thymus DNA