Abstract: OBJECTIVE To synthesize novel benzothiazole derivatives and investigate their antitumor activities. METHODS A series of 2-(arylpiperazine) acetamino-5-substituted-benzothiazole compounds were synthesized from 3-substituted anilines, and their antitumor activities were evaluated in vitro by the standard MTT assay. RESULTS Twelve novel benzothiazole derivatives were synthesized and their structures were confirmed with 1H-NMR, ESI-MS and elemental analysis. CONCLUSION Most of the target compounds showed antitumor activities against the tested tumor cells, and some compounds were comparable with that of 5-FU.