Electrostatic potentials of camptothecin and its analogues

In order to understand the influences of the modification of E-ring on the main frame of camptothecin (CPT), studies of the E-ring modification resulted changes in the stability and the electrostatic potential around the main frame of CPT were performed by the density functional theory. The results of present study indicate that the stability of the close-ring lactone form of CPT and homocamptothecin (hCPT) is similar to their open-ring hydroxylate forms, especially when in aqueous solutions. As an E-ring-modified CPT analogue, hCPT has essentially the same electrostatic potential (ESP) as CPT around the main frame (from A- to D-ring). However, the electrostatic potentials of the open-ring compounds are more negative around the main frame than that of CPT. The changes in the ESP of the CPT derivatives are found to be correlated with the corresponding dipole moments. Since electrostatic potential could influence the π–π stacking pattern between CPT (and its analogues) and the DNA bases, present study suggests that this π–π interaction of the open-ring forms of CPT and hCPT might be different from that of the close-ring lactone form. The information revealed in this study sheds light on the developments of new CPT-type antitumor drugs.