TQFL13, a novel synthetic derivative of thymoquinone (TQ), is more capable of inhibiting breast cancer progression than TQ.

Thymoquinone (TQ) is a bioactive component derived from Nigella Sativa seeds, and its anticancer properties have been well-documented. Our preliminary studies have also shown that the effective concentration of TQ against breast cancer (BC) is slightly high, indicating a need for chemical modification and optimization of the TQ compound. To address this, we designed and synthesized numerous TQ derivatives and conducted in-depth studies on the 13th derivative, TQFL13 from our laboratory. We found that, in BC cell lines, TQFL13 is more sensitive than that of TQ. The acute toxicity of TQFL13 in mice is significantly lower than that of TQ. We also discovered that TQFL13 impacts the progression of BC by affecting various cellular processes, including growth, invasion, migration, cell cycle, and apoptosis. Furthermore, treatment with TQFL13, it was found to inhibit the growth and metastasis of tumor allograft derived from mouse cancer cells 4 T1, and exhibit lower toxicity compared to TQ. Mechanically, TQFL13 is involved in signaling pathways in cell apoptosis and cell cycles by reducing PARP and BCL-2, CyclinB1, CyclinD1, and p53 levels as well as increasing BAX and phosphorylated p53 (ser15) levels in both BT549 and MDA-MB-231 cells. Taken together, these research findings imply that TQFL13, as a derivative of TQ, exerts a high inhibitory capability on BC cells with lower toxicity than TQ, indicating its potential for practical applications.