A series of 3-aryl/hetarylquinoxaline-2-carbonitrile-1,4-dioxides was synthesized and evaluated against breast cancer cell lines in normoxia and hypoxia. Selected compounds in this series demonstrated better cytotoxicity and comparable hypoxia selectivity than tirapazamine. In contrast to Dox, quinoxaline-1,4-dioxides showed potent cytotoxicity against different MDR cells. Compound 2g inhibits of cancer cell growth through p53-independent mechanisms. Our results showed that compound 2g sensitized MCF-7 cells to metformin in hypoxia. Treatment with 2g results in the increase of ROS accumulation in cancer cells. Compound 2g can be considered as the lead compound for further anticancer drug design, evaluation, and development of new potent antitumor agents.

assay using flow cytometry. Data analysis was done using the software CellQuestPro. Results and discussions Our study results demonstrated that the methanol extract of Holothuria scabra exhibited cytotoxic activity through inhibiting the growth of T47D cancer cells in a dose-dependent manner, start from 50 mg/mL until 500 mg/ mL, with IC 50 value of 152.98 mg/mL. The methanol extract of Holothuria scabra was able to stimulate 99% cancer cells to undergo apoptosis. This data warrant for further investigation on that apoptotic mechanism. The investigation is important to support cancer therapeutical strategies that focus on inducing cell death to overcome apoptosis resistance, one of the most important hallmark of cancer. Conclusion The methanol extract of Holothuria scabra contains a promising anti-cancer agent that possesses cytotoxic and apoptotic effects on breast cancer cells.