Synthesis and biotesting of new carrier prodrugs of 2-methoxyestradiol

To overcome the metabolic instability of anticancer agent 2-methoxyestradiol, two its dichloroacetylated prodrugs and three new control compounds have been synthesized and evaluated in different in vitro assays with cancer cells A549 and MCF-7. Both prodrugs demonstrated an intrinsic cytotoxicity to A549 cells with no effect on the cellular microtubule network. Molecular modeling has revealed putative weak halogen bond formation of 17-O-dichloroacetylated 2-methoxyestradiol with GTP in the a-tubulin subunit.