Synthesis and potential antineoplastic activity of dehydroabietylamine imidazole derivatives

脱氢枞胺咪唑衍生物的合成及其潜在的抗肿瘤活性

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Abstract

To seek more efficient and lower toxicity anticancer compounds, several imidazole combining dehydroabietylamine derivatives including organic salts (L (1) -L (2) ) and amides (L (3) -L (5) ) 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 (L (0) ). For MCF-7 cells, L (2) (0.75 μM) and L (5) (2.17 μM) had higher anti-MCF-7 activity than L (0) and DOX. For A549 cells, L (1) (1.85 μM) and L (2) (4.37 μM) had higher anti-A549 activity than L (0) ; in particular, the IC(50) value of L (1) was much lower than that of DOX. Among these investigated compounds, L (2) and L (5) had lower IC(50) 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, L (1) and L (2) could suppress cancer cell proliferation by inducing apoptosis. L (1) -L (5) could bind with DNA through intercalation.

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