Acridine-psoralen amines and their interaction with deoxyribonucleic acid

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Abstract
A series of novel compounds in which a 9-acridinyl nucleus is linked to a psoralen [dermatological drugs] nucleus in the 5- or 8-position via polyamines was prepared and examined. Their reversible binding to bovine DNA and their irreversible binding to DNA and DNA cross-linking upon irradiation with UV-A light were examined. They were all less efficiently photoreactive than 8-methoxypsoralen (8-MOP), both in cross-linking and photobinding to DNA, whereas the ratio between their photobinding and cross-linking was 40-400 times that of 8-MOP. Compounds in which the linker was attached to the 5-position in psoralen showed smaller cross-linking and photobinding efficiencies and larger ratios between photobinding and cross-linking than those of psoralens attached in the 8-position. This strongly indicates that the 9-substituents of the acridines are oriented toward the minor groove. Flow linear dichroism studies showed that the compounds were DNA intercalating with the acridine moiety, whereas the psoralen moiety in no case was clearly intercalating. This conclusion was further supported by viscometry which also strongly indicated monointercalation.