Synthesis, photophysical properties, and nucleic acid binding of phenanthridinium derivatives based on ethidium

A series of substituted phenanthridine derivatives has been synthesized by converting the amines at the 3- and 8-positions of ethidium bromide into guanidine, pyrrole, urea, and various substituted ureas. The resulting derivatives exhibit unique spectral properties that change upon binding nucleic acids. The compounds were analyzed for their ability to inhibit the HIV-1 Rev-Rev Response Element (RRE) interaction, as well as for their affinity to calf thymus DNA. One derivative (3,8-bis-urea-ethylenediamine- 5-ethyl- 6-phenylphenanthridinium, trifuroracetate) has an enhanced affinity and specificity for HIV-1 RRE as compared to ethidium bromide. These results indicate that the nucleic acid affinity and specificity of an intercalating agent can be tuned by synthetic modification of its exocyclic amines. (C) 2003 Elsevier Ltd. All rights reserved.