Abstract: In order to study the relationship between the structure and antimalarial activity of artemisinin and its analogues,the density functional theory (DFT) B3LYP method with 6-31G* basis set was used to calculate the geometries and properties of artemisinin and its analogues.The properties of the artemisinin and its analogues have been discussed in detail based on their molecular structures,Wiberg bond indexes,solvation energies,dipole moments and electrostatic potentials (ESPs).The results showed that the endoperoxy bridge on the seven-membered ring,the ether oxygen bond and six-member ring lactone structure were the most active sites for antimalarial activity of artemisinin and its analogues.The more negative electrostatic potential of the endoperoxy bridge,the stronger interaction between artemisinin and heme,and the stronger anti-malarial activity of the molecules would be.As a result,the order of antimalarial activity of the four drug molecules was predicted as:artemisinin < artemisinin < artesunate < artesunate,which was consistent with the experimental results.

Key words: artemisinin, antimalarial activity, density functional theory (DFT), electrostatic potentials (ESPs)