Synthesis, In Vitro, and In Vivo Investigations of Pterostilbene-Tethered Analogues as Anti-Breast Cancer Candidates

Pterostilbene has been found to be an active scaffold with anti-breast cancer (BC) action. In this study, fourteen pterostilbene-tethered analogues ( - ) were prepared and screened in vitro against MDA-MB-231 and MCF-7 cells. Meanwhile, their structures were characterized using H-NMR, C-NMR, and HRMS (ESI) spectroscopy techniques. Among them, analogue displayed the most potent anti-proliferation effect on MDA-MB-231 (IC = 10.39 μM) and MCF-7 cells (IC = 11.73 μM). Furthermore, the meaningful structure-activity relationships suggested that the introduction of a saturated six-membered nitrogen heterocyclic ring into the side chain favored anti-BC capacity. Biological observations indicated that could cause the typical morphological changes in apoptosis, namely an increase in reactive oxygen species level and a loss of mitochondrial membrane potential in BC cells. Importantly, could induce mitochondrial-mediated apoptosis by regulating the expression of caspase-related proteins. Consistent with the results of our in vitro study, apparently inhibited tumor growth in MDA-MB-231 xenograft mice without obvious toxicity. These findings revealed that is expected to be a promising anti-BC lead compound that merits further investigations.