DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play important essential genome functions, including DNA replication and transcription. Aberrant topoisomerases cause genome instability and a wide range of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable anticancer drugs, such as camptothecin. It has been previously shown that artemisinin, a sesquiterpene lactone from L. also known as , possesses anti-cancer effects and one of its derivatives, artesunate inhibits Topo 2. In this study, we evaluated artemisinin and 40 derivatives as potential Topo 1 inhibitors at first by molecular docking analyses. Five compounds that showed comparable binding energies and similar docking poses were selected for cytotoxicity test and Comet assay for DNA damage. WWLL-013, WWLL-022, and WWLL-1098 showed the lowest binding energy also induced DNA damage in the Comet assay. CMK-0298 and CMK-0398 intercalated into DNA and induced mild DNA damage. All selected compounds, WWLL-013 in particular, were more cytotoxic toward the rat tumor cells than to the normal cells. In conclusion, the artemisinin derivatives such as CMK-0298, CMK-0398, WWLL-013, WWLL-022, and WWLL-1098 can be further developed as Topo 1 inhibitors.