Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH₂ Core and Evaluation of Their Anticancer Activity

• Main Authors: Nalin Seixas (Author), Bruno B. Ravanello (Author), Ibrahim Morgan (Author), Goran N. Kaluđerović (Author), Ludger A. Wessjohann (Author)
• Format: Book
• Published: MDPI AG, 2019-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and solubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine) (PAMAM-NH₂) dendrimers with the simultaneous introduction of lipidic (<i>i</i>-Pr) and cationic (⁻NH₂) or anionic (⁻COOH) groups. Standard viability assays were used to evaluate the anticancer potential of the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well as non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity against PC-3 cells was considerably improved when both chlorambucil and ⁻NH₂ (cationic) groups were present on the dendrimer surface (<b>1b</b>). Additionally, this dendrimer showed activity only against the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts significantly. The cationic chlorambucil-dendrimer <b>1b</b> blocks PC-3 cells in the G2/M phase and induces caspase independent apoptosis.

Item Description

1999-4923
10.3390/pharmaceutics11020059