Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-07, Vol.26 (14), p.4302
• Main Authors: Sun, Xiao-Long, Zhu, Mei-Lin, Dai, Yi-Qun, Li, Hong-Mei, Li, Bo-Han, Ma, Hui, Zhang, Chang-Hao, Wu, Cheng-Zhu
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antitumor activity; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell growth; Chemotherapy; Chromatography; Cytotoxicity; Experiments; Gelatinase A; Gelatinase B; Hypoxia; Hypoxia-inducible factor 1a; invasion; magnolol; Medical prognosis; Metastasis; migration; Natural products; Optimization; semi-synthesis; Semisynthesis; Tumor cell lines; Western blotting; Wound healing
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26144302

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.