Novel magnolol-sulforaphane hybrids as potent antitumor agents: synthesis and biological characterization

The natural product-based hybrid strategy is a promising approach for innovative drug discovery. Leveraging the privileged architecture of sulforaphane-a prominent anticancer natural product-we engineered a novel library of magnolol-sulforaphane molecular hybrids for antitumor evaluation through a concise synthetic strategy for the pharmacophore of sulforaphane (SFN), culminating in the identification of CTNPC8 as a promising anticancer compound. Notably, CTNPC8 not only displays exceptional broad-spectrum anticancer activity with potency surpassing both parent compounds and cisplatin, but also exhibits potent in vitro efficacy against the challenging nasopharyngeal carcinoma (NPC) cell model. Mechanistic studies in nasopharyngeal carcinoma models reveal that CTNPC8 triggers mitochondrial-mediated apoptosis through regulating ROS generation and induces G₂/M phase arrest. Transcriptomic profiling coupled with validation experiments reveals that CTNPC8 exerts its anti-NPC activity primarily by modulating the Akt/mTOR pathway. The present study provided a valuable strategy for discovering new antitumor agents through hybrid molecular design, nominating CTNPC8 as a promising hit compound for anti-NPC research.