Design, Synthesis, and Bioactivity Evaluation of Novel Rosin Diterpenoid Derivatives as Potential Anti‐glioma Agents

Abstract

AbstractGlioma is the most common brain tumor and its treatment options are limited. Abietic acid and dehydroabietic acid are tricyclic diterpenoid oxygen compounds with strong lip solubility and anti‐glioma activity. In this study, novel rosin diterpenoid derivatives were designed and synthesized using abietic acid and dehydrogenated abietic acid as lead compounds and their activities against T98G, U87MG, and U251 cells were evaluated by CCK‐8 methods. The in vivo activity of compounds with stronger activity in vitro was preliminarily studied through the Zebrafish model. The results showed that the IC50 values of B6, B8, B10, and B12 were 11.47 to 210.6 μM, which were exhibited higher antiproliferative potency against T98G, U87MG, and U251. The scratch experiment showed that B12 inhibited the migration of T98G in a time‐dependent and concentration‐dependent manner. The results of in vivo activity further explained that B12 could inhibit the proliferation of the T98G. The pKa values of B6, B8, B10, and B12 were 7.17 to 7.35, which were within the ideal range of glioma drugs. The ADME predictions indicated that these derivatives could pass through the blood‐brain barrier. In addition, molecular docking primarily explained interaction between compounds and protein. These results suggested that B12 should be a promising candidate that merits further attention in the development of anti‐glioma drugs.