Spectrophotometric studies on the thermodynamics of the DS-DNA interaction with irinotecan for a better understanding of anticancer drug-DNA interactions

The ds-dna binding properties of irinotecan (cpt-11) including binding constant,thermodynamic parameter,and thermal denaturation (tm) have been systematically studied by spectrophotometric methods. the binding of cpt-11 to ds-dna is quite strong as indicated by its remarkable hypochromicity and equilibrium binding constant (kb). the van't hoff plot of 1/t versus ln kb suggests that the cpt-11 binds endothermically to ct-dna which is characterized by large positive enthalpy and entropy changes. according to the polyelectrolyte theory,the charge release (z),when ct-dna interacts with cpt-11,is +0.98,which corresponds very well to the one positive charge carried by cpt-11. the kb at a low concentration of salt is dominated by electrostatic interaction (98.5%) while that at a high concentration of salt is weakly controlled by nonelectrostatic processes (19.0%). a moderate stabilization of the double helix ds-dna occurs when cpt-11 binds to ds-dna as indicated by the increase in tm of ct-dna by approximately 15°c in the presence of cpt-11. the cpt-11 is stabilized by intercalation in the dna (binding constant,k [irinotecan-dna] = 5.8 × 104 mol-1 l) and displaces the nr dye from the nr-dna complex (k [nr-dna] = 2.7 × 104 mol-1 l) in a competitive reaction. © 2013 reza hajian and tan guan huat.