Role of structural components of the 2-methoxyestradiol—chlorambucil conjugate in microtubule stabilization

The conjugate of 2-methoxyestradiol, a ligand for the cell protein tubulin, with two molecules of chlorambucil, known as a DNA-alkylating agent, is capable of blocking the dynamics of tubulin-based microtubules at concentrations of 10–100 µmol L −1 , by stabilizing them without changing their structure. Three analogs of this conjugate, which do not contain chloroethylamino and/or methoxy groups at C(2), were synthesized. At these concentrations, these analogs have another, inhibitory or combined, effect on the microtubule polymerization. Based on the molecular modeling results, the binding site of the initial conjugate in tubulin was proposed.