Synthesis and potential antineoplastic activity of dehydroabietylamine imidazole derivatives

Abstract

To seek more efficient and lower toxicity anticancer compounds, several imidazole combining dehydroabietylamine derivatives including organic salts (L¹–L²) and amides (L³–L⁵) were synthesized. Their antineoplastic activity against HeLa (cervix), MCF-7 (breast), A549 (lung) and HepG2 (liver) cells and HUVECs (umbilical vein, normal cells) in vitro were evaluated by MTT assay. The results unequivocally showed that nearly all compounds had better antineoplastic activity and lower toxicity than dehydroabietylamine (L⁰). For MCF-7 cells, L² (0.75 μM) and L⁵ (2.17 μM) had higher anti-MCF-7 activity than L⁰ and DOX. For A549 cells, L¹ (1.85 μM) and L² (4.37 μM) had higher anti-A549 activity than L⁰; in particular, the IC₅₀ value of L¹ was much lower than that of DOX. Among these investigated compounds, L² and L⁵ had lower IC₅₀ values (0.75 μM and 2.17 μM) against MCF-7 cells and lower toxicity, which suggested that they may be potential future anticancer drugs. In addition, L¹ and L² could suppress cancer cell proliferation by inducing apoptosis. L¹–L⁵ could bind with DNA through intercalation.