Studies on DNA binding of caffeine and derivatives: evidence of intercalation by DNA-unwinding experiments.
Caffeine and derivatives are compounds with pleiotropic effects on the genetic material which are supposed to originate from drugs binding to DNA. Here we show, by using two different topological methods, that methylated oxypurines, at biologically relevant concentrations, unwind DNA in a fashion similar to known intercalators. Methylated oxypurines could be ranked by decreasing unwinding potency: 8-methoxycaffeine greater than 8-ethoxycaffeine greater than 8-chlorocaffeine greater than caffeine greater than theophylline. These findings confirm, with a different assay, interaction of caffeine with DNA and add additional support to an intercalative mode of binding of these drugs to DNA.
Tornaletti
S
S
Istituto di Genetica Biochimica ed Evoluzionistica del C.N.R., Pavia, Italy.
Russo
P
P
Parodi
S
S
Pedrini
A M
AM
D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000187:drug effects*; D004270:DNA, Circular / Q000187:drug effects; D007364:Intercalating Agents / Q000494:pharmacology; D010957:Plasmids / Q000187:drug effects
D004269:DNA, Bacterial; D004270:DNA, Circular; D007364:Intercalating Agents; D002110:Caffeine