Novel Dehydroabietylamine C-Ring Schiff Base Derivatives: Synthesis, Antiproliferative activity, DNA binding and Molecular docking.

A series of Dehydroabietylamine (DHAA) C-ring Schiff derivatives, L3-L20, were synthesized and their in vitro cytotoxic activity against the human tumor cell lines cervix HeLa, breast MCF-7, lung A549, liver HepG2, and the nonmalignant cell line umbilical vein HUVEC was investigated. Most of the compounds showed varying degrees of anticancer activity against HeLa cell lines while demonstrating lower toxicity to normal HUVEC cells compared to DHAA and doxorubicin (DOX), especially compound L19, which not only enhanced the anticancer activity of DHAA, but also significantly reduced the toxicity to normal cells, achieving a selectivity index (SI) 118 times higher than that of DHAA and 245 times higher than that of DOX. In addition, compound L19 induced apoptosis in HeLa cells in a dose-dependent manner and arrested the cell cycle in S phase. Spectroscopic experiments and molecular docking results showed that there was a strong interaction between the compounds and DNA. All these results indicate that the introduction of Schiff base structure on the C-ring of DHAA is an effective strategy for enhancing its selectivity, providing new insights for the design of DHAA-based anticancer compounds.