Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents.

[Display omitted] • 30 β -carboline-(phenylsulfonyl)furoxan hybrids were designed and synthesized. • Target molecules showed potent anti-breast cancer proliferative activity. • 13h displayed potent antiproliferative activity against MDA-MB-231 cells. • 13h suppressed the migration and invasion of MDA-MB-231 cells. • ROS generation and activating DNA damage involved in 13h -induced apoptosis. The cytotoxicity properties of the β -carboline alkaloids have been broadly investigated. However, the potential application of β -carbolines was hindered due to the moderate activity in cancer. In the present study, thirty β -carboline-(phenylsulfonyl)furoxan hybrids (11a–j , 12a–j and 13a–j) were designed and synthesized through esterification and amidation reaction strategy, and their inhibitory activities against the human breast cancer cell lines MCF-7 and MDA-MB-231 were evaluated by CCK-8 assay. Biological evaluation presented that the most promising amide derivative 13h , substituted with p -methoxyphenyl group at position 1, generated high concentration of NO and evidently depressed the MCF-7 (IC 50 = 0.89 μM) and MDA-MB-231 (IC 50 = 0.62 μM) cells proliferation. Particularly, the wound healing and transwell assays demonstrated that 13h significantly inhibited the migration and invasion of MDA-MB-231cells. Furthermore, the preliminary mechanisms studies indicated that 13h induced G2/M phase arrest and apoptosis possibly causing by ROS accumulation and ROS-mediated DNA damage. Based on these considerations, 13h may be a promising antimetastatic agent for breast cancer, which is noteworthy for further exploration. [ABSTRACT FROM AUTHOR]