Anti-breast cancer sinomenine derivatives via mechanisms of apoptosis induction and metastasis reduction.

Sinomenine, a morphinane-type isoquinoline-derived alkaloid, was first isolated from stems and roots of (Miq.) in 1920. Later discovery by researchers confirmed various essential biological efficacy sinomenine exerted and . In this study, a series of 15 sinomenine/furoxan hybrid compounds were designed and synthesised in search of a TNBC drug candidate. Some of the target compounds exhibited strong antiproliferative activities against cancer cell lines, especially for TNBC cells, compared to positive controls. Among them, hybrid exerted superior cytotoxic effects on cancer cell lines with exceptionally low IC (0.82 μM) against MDA-MB-231 cells with the highest safety index score. Further studies in mechanism displayed that could induce an S phase cell cycle arrest, stimulate apoptosis in MDA-MB-231 cells, disrupt mitochondrial membrane potential and exert a genotoxic effect on DNA in cancer cells. In addition, also notably inhibited MDA-MB-231 cells in both migration, invasion and adhesion.