Design, Synthesis, Molecular Docking, and Biological Evaluation of Tanshinone IIA Derivatives as Antibreast Cancer Agents

In order to explore the effect of amino introduction of Tanshinone IIA on the antitumor activity, 18 novel N-substituted tanshinone IIA derivatives were synthesized and investigated for their anti-proliferative activity in a panel of cancer cell lines. The biological evaluation of antiproliferative assay led to the discovery of compound TA-16 with a highly potent cytotoxic effect using cervical, colon, liver and breast cancer cells, with IC₅₀ = 1.25 µM against MCF-7 cell. The mechanistic studies indicated the ability of TA-16 in inducing apoptosis of MCF-7 cells through mitochondrial pathway and arresting the cell cycle at the G0/G1 phase. It exhibited significant anti-metastasis properties by inhibiting the expression of MMP-9 and MMP-2. Moreover, the cytotoxic study of compound TA-16 on the MCF-10A, a normal human breast epithelial cell line, further highlighted the potential of compound TA-16 as an anticancer agent for breast cancer with a selectivity index of 4.95. Molecular docking analyses confirmed the binding interaction between compound TA-16 and its target proteins, validating its mechanism of action and potential as a therapeutic agent for breast cancer.