Non-covalent binding of some phenothiazine drugs to DNA

The binding of a number of phenothiazine drugs (PHs) to calf thymus DNA was studied with equilibrium dialysis. The Scatchard plots reveal two types of binding. Relatively strong binding is observed at low PH concentration. For various PHs the apparent binding constants do not differ significantly, but the binding capacity of DNA varies with the 2-substituent: 2-chloro-PHs exhibit the highest extent of strong binding. For this binding type the DNA double-helix structure is essential, suggesting that (partial) intercalation of the PH-nucleus between two adjacent DNA base-pairs plays a role. At higher PH-concentrations the apparent binding constants become very small. In this PH-concentration range the structure of the side-chain of the PH appears to be of importance for the DNA-binding.Compounds with a piperazine ring in the side-chain show cooperative binding in which next to electrostatic interactions also formation of aggregates may be important.