Quinoline alkaloids are abundant in the Rutaceae, and many have exhibited 
cytotoxic activity. Because structurally related antitumor alkaloids such as 
camptothecin and fagaronine are known to function as intercalative topoisomerase 
poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve 
as intercalative topoisomerase inhibitors. To test this hypothesis 
theoretically, ten Stauranthus quinoline alkaloids were examined for potential 
intercalation into DNA using a molecular docking approach. Four of the alkaloids 
(stauranthine, skimmianine, 3',6'-dihydroxy-3',6'-dihydrostauranthine, and 
trans-3',4'-dihydroxy-3',4'-dihydrostauranthine) were able to intercalatively 
dock consistently into DNA. In order to probe the intermolecular interactions 
that may be responsible for intercalation of these quinoline alkaloids, density 
functional calculations have been carried out using both the B3LYP and M06 
functionals. M06 calculations indicated favorable pi-pi interactions between 
either skimmianine or stauranthine and the guanine-cytosine base pair. 
Furthermore, the lowest-energy face-to-face orientation of stauranthine with 
guanine is consistent with favorable dipole-dipole orientations, favorable 
electrostatic interactions, and favorable frontier molecular orbital 
interactions. Likewise, the lowest-energy face-to-face orientation of 
stauranthine with the guanine-cytosine base pair reveals favorable electrostatic 
interactions as well as frontier molecular orbital interactions. Thus, not only 
can quinoline alkaloids dock intercalatively into DNA, but the docked 
orientations are also electronically favorable.