Work

Novel Isolongifolenone-Based Caprolactam Derivatives as Potential Anticancer Agents via the p53/mTOR/Autophagy Pathway

Year: 2025

Type: article

Abstract: Isolongifolenone, a natural sesquiterpenoid widely used in food additives and perfume, demonstrates a range of biological activities. In this study, a series of isolongifolenone-based caprolactam derivatives (E1–E19) were designed, synthesized, and evaluated for their anticancer activities in vitro. Most of the synthesized compounds significantly inhibited the proliferation of cultured cancer cells. Compound E10, containing an m-trifluoromethyl group, demonstrated the strongest anti-proliferation activities against MCF-7 (IC50 = 0.32 µM), HepG2 (IC50 = 1.36 µM), and A549 (IC50 = 1.39 µM) cells. Moreover, E10 was shown to increase intracellular ROS, reduce mitochondrial function, and induce cancer cell apoptosis via the p53/mTOR/autophagy pathway. Together, these results indicate that compound E10 induced autophagy-associated cell apoptosis in MCF-7 cancer cells. Additionally, the antitumor activity of E10 was validated in a zebrafish MCF-7 xenograft model. The observation that E10 exhibits potent antitumor activity in both a three-dimensional (3D) cell culture model and the zebrafish xenograft model supports the development of E10 as a potential drug candidate for cancer therapy.

Source: Molecules

DOI: 10.3390/molecules30194013