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 (<b>L</b> ^<b>1</b> -<b>L</b> ^<b>2</b> ) and amides (<b>L</b> ^<b>3</b> -<b>L</b> ^<b>5</b> ) were synthesized. Their antineoplastic activity against HeLa (cervix), MCF-7 (breast), A549 (lung) and HepG2 (liver) cells and HUVECs (umbilical vein, normal cells) <i>in vitro</i> were evaluated by MTT assay. The results unequivocally showed that nearly all compounds had better antineoplastic activity and lower toxicity than dehydroabietylamine (<b>L</b> ^<b>0</b> ). For MCF-7 cells, <b>L</b> ^<b>2</b> (0.75 μM) and <b>L</b> ^<b>5</b> (2.17 μM) had higher anti-MCF-7 activity than <b>L</b> ^<b>0</b> and DOX. For A549 cells, <b>L</b> ^<b>1</b> (1.85 μM) and <b>L</b> ^<b>2</b> (4.37 μM) had higher anti-A549 activity than <b>L</b> ^<b>0</b> ; in particular, the IC₅₀ value of <b>L</b> ^<b>1</b> was much lower than that of DOX. Among these investigated compounds, <b>L</b> ^<b>2</b> and <b>L</b> ^<b>5</b> 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, <b>L</b> ^<b>1</b> and <b>L</b> ^<b>2</b> could suppress cancer cell proliferation by inducing apoptosis. <b>L</b> ^<b>1</b> -<b>L</b> ^<b>5</b> could bind with DNA through intercalation.