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 (2A-2N) were prepared and screened in vitro against MDA-MB-231 and MCF-7 cells. Meanwhile, their structures were characterized using 1H-NMR, 13C-NMR, and HRMS (ESI) spectroscopy techniques. Among them, analogue 2L displayed the most potent anti-proliferation effect on MDA-MB-231 (IC50 = 10.39 µM) and MCF-7 cells (IC50 = 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 2L 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, 2L could induce mitochondrial-mediated apoptosis by regulating the expression of caspase-related proteins. Consistent with the results of our in vitro study, 2L apparently inhibited tumor growth in MDA-MB-231 xenograft mice without obvious toxicity. These findings revealed that 2L is expected to be a promising anti-BC lead compound that merits further investigations.

Direct Alkylation of Quinoxalinones with Boracene-Based Alkylborate under Visible Light Irradiation.

An efficient synthesis of a variety of 3-alkyl quinoxalinones via C-H direct alkylation by photoredox catalysis between quinoxalinones and alkylborates is reported. A range of quinoxalinones was tolerated well. This visible-light photocatalysis reaction allows access to structurally diverse 3-alkyl quinoxalinones in good to excellent yields. The practicality of this protocol was demonstrated by the concise synthesis of a potential bioactive nonpeptide angiotensin II receptor antagonist.