Molecular design and synthesis of new heterobivalent compounds based on chlorambucil and colchicine

摘要

Two new heterobivalent molecules were designed by linking a DNA-alkylating agent chlorambucil with tubulin-targeting compound colchicine or its adamantyl containing C(7)derivative. Target compounds were synthesized via acid coupling with N-deacetylcolchicine. According to preliminary biotests, both conjugates caused microtubule depolymerization and strong tubulin clustering, and colchicine-chlorambucil conjugate was found to be one order of magnitude more potent and to exhibit some selectivity to A549 carcinoma cells.