Novel amino analogs of the trimethoxyphenyl ring in potent colchicine site ligands improve solubility by the masked polar group incorporation (MPGI) strategy

•A-ring amino derivatives of colchicine site ligands were designed and synthesized.•Amino groups improved solubility.•The most potent compounds elicit nM anti-proliferative activity against several human cancer cells.•Compounds act by microtubule disruption in cells, leading to G2/M cell cycle arrest and induction of apoptosis.•Docking studies at the colchicine site of tubulin support the design hypothesis and inform structure–activity relationships.