Synthesis of water-soluble dendrimers based on melamine bearing 16 paclitaxel groups

Org Lett. 2008 Jan 17;10(2):201-4. doi: 10.1021/ol7024907. Epub 2007 Dec 19.

Abstract

The design, synthesis, and characterization of triazine dendrimers derivatized with the anticancer agent paclitaxel are described. The precursor generation two dendrimer 1 is prepared in six linear steps in 64% overall yield and presents 16 amines and two groups for radioiodination. This macromolecule is subsequently derivatized with a paclitaxel conjugate to yield a generation three dendrimer, 2, which is then pegylated in two steps. The pegylated final products, 4a and 4b, with molecular weights of 46 and 77 kDa, respectively, solubilize paclitaxel in water. Pegylated dendrimer 4a is 30 wt % paclitaxel, 52 wt % PEG, and 18 wt % dendrimer. Target 4b is 18 wt % paclitaxel, 71 wt % PEG, and 11 wt % dendrimer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Dendrimers / chemical synthesis*
  • Molecular Structure
  • Paclitaxel / chemistry*
  • Polyethylene Glycols
  • Solubility
  • Triazines / chemistry*
  • Water

Substances

  • Antineoplastic Agents
  • Dendrimers
  • Triazines
  • Water
  • Polyethylene Glycols
  • melamine
  • Paclitaxel