Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents

A series of 1-benzyl-4,5,6-trimethoxyindoles was designed and prepared as a novel class of potent antimitotic agents acting through the colchicine binding site of tubulin. Compounds 10 and 11 showed excellent antiproliferative activity with mean IC₅₀ values of 26 and 27 n M, respectively, in a diverse set of human cancer lines from different organs, including a MDR+ line. They also displayed substantial antitubulin efficacy with IC₅₀ values of 3.5 and 2.6 μM, respectively, representing an improvement over colchicine (IG₅₀=4.3μM).