New salidroside-furoxan hybrids as potential agents inhibit triple-negative breast cancer

Salidroside (SAL) is a natural glycoside compound with various biological activities. Recent studies have shown that SAL exhibits certain therapeutic effects on triple-negative breast cancer (TNBC). To enhance the anti-TNBC activity, 15 SAL-furoxan hybrids were designed and synthesized. The anti-proliferative activities of all target compounds against four tumor cell lines (MDA-MB-231, MCF-7, BGC-823, and A549) and a normal human cell line (MCF-10A) were evaluated using the MTT assay. A12 demonstrated the most potent inhibitory activity on MDA-MB-231 cells (IC₅₀ = 14 nM), and lower toxicity compared to DOX (SI = IC_50(MCF-10A)/IC_{50(MDA-MB-231)}: 129.57 vs 1.01). Further research indicated that the anti-tumor mechanism of A12 involves the high amount of NO released in MDA-MB-231 cells and thereby induction of cells apoptosis.