Assessment of a bifendate derivative bearing a 6,7-dihydro-dibenzo[c,e]azepine scaffold as a potential anti-metastatic agent

Abstract

Multidrug resistance (MDR) and metastasis are major causes of mortality in patients with cancer. We recently reported a bifendate derivative bearing a dibenzo[c,e]azepine scaffold (4i) as a P-gp and BCRP-medicated MDR reversal agent. As a continuation of the previous research, its ability to inhibit cancer metastasis was investigated in MDA-MB-231 cells in the present work. Wound-healing and chamber migration assays showed that 4i could significantly attenuate the migration of MDA-MB-231 cells. Additionally, 4i obviously suppressed the invasive activity of MDA-MB-231 cells, thus displaying potential anti-metastasis activity. Preliminary mechanism studies indicated that the anti-metastasis activity of 4i was associated with the inhibitory effect on the activity and expression of MMP-2 and MMP-9. These results, together with the previous findings, suggest that compound 4i could be a promising lead for the development of novel anti-cancer agents with anti-MDR and metastatic activities.