Synthesis,characterization and biological activities of nitrogen-containing Combretastatin A-4 derivatives

Abstract The new compounds 6a-6d and 9a-12c were synthesized from starting material. The intermediate (E)-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl) acrylic acid was used to synthesis a series of combretastatin A-4(CA-4) analogues containing nitrogen atoms and nitrogen heterocycles were synthesized by condensation reaction, reduction reaction, hydrolysis reaction and Crutius rearrangement. All new compounds were characterized by nuclear magnetic resonance and mass spectrometry. The antitumor cytotoxicity of a series of newly synthesized compounds were evaluated in vitro toward the cell line of hepatoma cell with erianin as positive control. Amoung all the compound, 6b demonstrated the most antitumor activity with the inhibition rate 93.85%.