A large number of antimitotic drugs, derived from natural sources or chemically synthesized, have been identified and shown to interfere with the tubulin system. Inhibition of tubulin polymerization is among the important targets useful in the cancer therapy. The present work reports the synthesis of some novel quinoline derivatives bearing a trimethoxyphenyl moiety. The trimethoxybenzene moiety has been reported to be crucial to obtain relevant cytotoxic and antitubulin responses. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Several compounds showed interesting cytotoxic activities compared to the used reference drug.