Nitro-Substituted Benzylic Organochalcogenides as Anticancer Agents: Unravelling the Multifaceted Pathways to Combat Triple-Negative Breast Cancer

Organochalcogens exhibit promising chemotherapeutic potential against several cancer types. However, their ability to simultaneously target interconnected oncogenic signaling networks remains mostly unexplored. Herein, we report 4-nitro-substituted benzylic diselenide <b>7</b>, which exhibits concerted inhibition of Akt/mTOR and ERK pathways with the suppression of NF-κB-mediated inflammation and invasiveness against the highly aggressive triple-negative breast cancer MDA-MB-231 cells. Detailed mechanistic investigations illustrated that diselenide <b>7</b> induces ROS, leading to DNA damage, mitochondrial dysfunction, and consequent suppression of the Akt/mTOR-ERK1/2 signaling axis, leading to cellular death. Furthermore, the potency of <b>7</b> was validated in Swiss albino mice bearing breast adenocarcinoma, with a markedly reduced tumor volume, downregulation of VEGF/MMP-9 expressions indicating impaired angiogenesis/metastasis, and the expansion of life span. This work exemplifies distinctive mechanistic insights into the multitargeting agent diselenide <b>7</b>, highlighting its potential as an anticancer therapeutic and paving the way for the development of small-molecule organoselenium compounds for the effective treatment of cancer.