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 special complex formed with a covalently closed circular (ccc) form of plasmid DNA. The exact target in this macromolecule, however, was not clarified until recently. Caffeine and the chemically similar guanosine-5'- monophosphate (GMP) could compete with the antiplasmid effect of promethazine, showing that promethazine or other phenothiazines preferentially bind to xanthine type molecules. Among the xanthines, GMP was more effective at complex-forming 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 region 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 anticancer activity.
Miskolci
C
C
Institute of Microbiology, Albert Szent-Györgyi Medical University, Dóm Tér 10, H-6720, Szeged, Hungary.
Labádi
I
I
Kurihara
T
T
Motohashi
N
N
Molnár
J
J
D001665:Binding Sites; D002110:Caffeine / Q000494:pharmacology; D003596:Cytosine / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects; D006147:Guanine / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000494:pharmacology; D010640:Phenothiazines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects*; D019820:Xanthine / Q000737:chemistry
D004269:DNA, Bacterial; D010640:Phenothiazines; D019820:Xanthine; D002110:Caffeine; D006147:Guanine; D006157:Guanosine Monophosphate; D003596:Cytosine