Design, synthesis and biological evaluation of Nrf2 modulators for the treatment of glioblastoma multiforme

We used virtual screening technology to discover and identify a compound, pinosylvin, that can effectively inhibit GBM proliferation. Pinosylvin exhibits strong hydrogen bonding and Π-Π interactions with Nrf2. Cellular experiments showed that pinosylvin effectively reduced the proliferation of U87 tumor cells by regulating Nrf2 and showed stronger inhibitory activity than temozolomide. [Display omitted] Glioblastoma multiforme (GBM) is a prevalent primary brain tumor. However, no specific therapeutic drug has been developed for it. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor involved in the cellular response to oxidative stress. Numerous studies have demonstrated that Nrf2 plays a pivotal role in GBM angiogenesis, and inhibiting Nrf2 can significantly enhance patient prognosis. Using virtual screening technology, we examined our in-house library and identified pinosylvin as a potential compound with high activity. Pinosylvin exhibited robust hydrogen bond and Π-Π interaction with Nrf2. Cell experiments revealed that pinosylvin effectively reduced the proliferation of U87 tumor cells by regulating Nrf2 and demonstrated greater inhibitory activity than temozolomide. Consequently, we believe that this study will offer valuable guidance for the future development of highly efficient therapeutic drugs for GBM.