Aim To design and synthesize a series of 2-（E）-（4-cyclopentyloxy-3-methoxylbenzylidene）cyclopentanone derivatives, and to determine their antitumor activities in vitro. Method The target compounds were synthesized. Their antitumor activities were assayed using human hepatic carcinoma ceil line （Bel-7402） and human oral cavity epidermis squamoceilular carcinoma cell line （KB）. Results Five compounds were obtained. Three of them were not reported in the literature and their chemical structures were confirmed by IR, ^1H NMR, MS and elemental analysis. Preliminary screening results showed that compound 5 possessed better biological activity with IC50 1.62 μmol·L^-1 against Bel-7402 and 8.04 μmol·L^-1 against KB, but much weaker than 5- Fluorouracil. Conclusion Mannich base derivatives of 2-（E）-（4-cyclopentyloxy-3-methoxylbenzylidene）cyclopentanone exhibited some antitumor activities.
