Design, Synthesis, and Anti‐Glioma Activity Evaluation of Dehydroabietic Acid Derivatives

Abstract Dehydroabietic acid (DHAA) is a common natural product with a broad range of biological activities. In previous research, our group identified a range of dehydroabietic acid derivatives with strong anti‐glioma activity. In order to search for better anti‐glioma drugs candidates, new chalcone derivatives A1‐A10 and B1‐B10 were designed and synthesized in this study. The antiproliferative activity of these derivatives against U87 glioma cells was tested by CCK‐8 assay, in which A10 has the best IC 50 value of 11.39 µM. Scratch and cloning studies further confirmed that A10 strongly inhibited the proliferation and colony‐forming activity of U87 cells. The antiproliferative activity of A10 on U87 cells showed some concentration dependence manner and the pKa values of A10 were within the desirable range of anti‐gliomas drugs. In addition, molecular docking revealed hydrogen bonding interaction was formed between A10 and the target protein. These results suggest that A10 may be a promising DHAA‐derived lead compound that deserves further strategic optimization in search of the anticancer candidates against glioma.