Guanine-cytosine rich regions of plasmid DNA can be the target in anti-plasmid effect of phenothiazines

The antiplasmid effects of promethazine on E. coli is the consequence of sp ecial complex formed with a covalently closed circular (ccc) form of plasmi d DNA. The exact target in this macromolecule, however, was not clarified u ntil recently. Caffeine and the chemically similar guanosine-5'- monophosph ate (GMP) could compete with the antiplasmid effect of promethazine, showin g that promethazine or other phenothiazines preferentially bind to xanthine type molecules. Among the xanthines, GMP was more effective at complex-for ming than adenosine-5'-monophosphate (AMP). In addition, the Z-DNA was more susceptible than B-DNA. Therefore, one could suppose that guanine-cytosine (G-C) rich regions have higher affinity than adenine-thymine (A-T) rich re gion on phenothiazines. Because the G-C rich regions have a special role in the DNA stability via three hydrogen bonds, we suppose that these regions could have a key role in some biological effects such as antiplasmid and an ticancer activity. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.