Breast cancer is one of the most common tumors in females. The therapeutic resistance of breast cancer has motivated the development of new agents for prevention and treatment. For the present study, several compounds were designed and analyzed for their antitumor activity in many cancer cell lines. 4-(3,4,5-Trimethoxyphenoxy) benzoic acid (compound 1) and its derivatives were selected for studying the anti-proliferative and cytotoxic effects on five human cancer cell lines. Results indicated that compounds 1 and 2 significantly suppressed the cell viability of MCF-7 and MDA-MB-468 cancer cells. However, compounds 1 and 2 had only minor effects on HepG2, Huh-7, and Hela cells. Moreover, compounds I and 2 exhibited a novel anti-tumor activity through the induction of cell-cycle arrest at G(2)/M and apoptosis in MCF-7 and MDA-MB-486 breast cancer cells. Both compounds reduced colony-forming ability in MCF-7 cells. Flow cytometric analysis indicated that caspase-3 activity was increased in response to treatment with compounds 1 and 2. Taken together, these findings suggest that the novel compounds 1 and 2 are potential anticancer agents with clinical promise for breast cancer therapy.