Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and\nsolubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine)\n(PAMAM-NH2) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (â??NH2)\nor anionic (â??COOH) groups. Standard viability assays were used to evaluate the anticancer potential\nof the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well\nas non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity\nagainst PC-3 cells was considerably improved when both chlorambucil and â??NH2 (cationic) groups\nwere present on the dendrimer surface (1b). Additionally, this dendrimer showed activity only\nagainst the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts\nsignificantly. The cationic chlorambucil-dendrimer 1b blocks PC-3 cells in the G2/M phase and\ninduces caspase independent apoptosis.
Loading....